1
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Fu Y, Wang T, Ge X, Wen H, Fei Y, Li M, Luo Z. Orally-deliverable liposome-microgel complexes dynamically remodel intestinal environment to enhance probiotic ulcerative colitis therapy via TLR4 inhibition and tryptophan metabolic crosstalk. Biomaterials 2025; 321:123339. [PMID: 40233710 DOI: 10.1016/j.biomaterials.2025.123339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 03/21/2025] [Accepted: 04/10/2025] [Indexed: 04/17/2025]
Abstract
Probiotics emerges as a promising option for ulcerative colitis (UC) treatment, but its application remains challenging due to insufficient colon-targeted delivery efficiency and survival against the inflammation-associated intestinal oxidative stress. To address these issues, here we report a supramolecular liposome-microgel complex (SLMC) incorporated with Bacillus subtilis spores (BSSs) and dexamethasone (DEX) for orally-deliverable probiotic UC therapy. Specifically, BSSs and cholesterols were conjugated with gelatin via diselenide ligation to prepare microgels, followed by supramolecular complexation with UC-targeted DEX-loaded liposome via microfluidic engineering. The orally-administered SLMC efficiently accumulated in UC-affected colonic sites to release BSSs and DEX. DEX elicited rapid anti-inflammatory effect to reduce ROS generation, which cooperated with the ROS consumption by spore germination and diselenide cleavage to orchestrate an anaerobic intestinal microenvironment, thus promoting Bacillus subtilis colonization to restore gut homeostasis and initiate anti-inflammatory microbiota-macrophage metabolic crosstalk. Indeed, in vivo analysis showed that the SLMC treatment markedly inhibited pro-inflammatory TLR4-NF-κB signaling activities in mucosal macrophages through localized DEX delivery and boosting tryptophan metabolite production, leading to robust and durable UC abolishment. This study offers a practical approach for improving UC treatment in the clinic.
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Affiliation(s)
- Yuanyuan Fu
- School of Life Sciences, Chongqing University, Chongqing, 400044, China
| | - Ting Wang
- School of Life Sciences, Chongqing University, Chongqing, 400044, China
| | - Xinyue Ge
- School of Life Sciences, Chongqing University, Chongqing, 400044, China
| | - Hong Wen
- Department of General Surgery, Xinqiao Hospital, Army Medical University, No. 183 Xinqiao Road, Chongqing, 400037, China
| | - Yang Fei
- School of Life Sciences, Chongqing University, Chongqing, 400044, China
| | - Menghuan Li
- School of Life Sciences, Chongqing University, Chongqing, 400044, China.
| | - Zhong Luo
- School of Life Sciences, Chongqing University, Chongqing, 400044, China.
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2
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Gao L, Liu Y, Ye L, Liang S, Lin J, Zeng J, Lei L, Huang Q, Wan Y, Zhang B. Metal ion coordinated tea polyphenol nanocoating for enhanced probiotic therapy in inflammatory bowel disease. Biomaterials 2025; 321:123323. [PMID: 40215650 DOI: 10.1016/j.biomaterials.2025.123323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 03/18/2025] [Accepted: 04/04/2025] [Indexed: 05/04/2025]
Abstract
Probiotics encapsulated with metal-phenolic networks (MPNs) present a promising approach for treating inflammatory bowel diseases (IBD). However, current MPN systems predominantly use tannic acid (TA) as the phenolic source, with limited exploration of other polyphenols, and face challenges in long-term stability and biocompatibility. Herein, three alternative tea polyphenols, gallic acid (GA), epigallocatechin (EGC) and epigallocatechin gallate (EGCG), were coordinated with ferric ions, to fabricate MPN-coated Lactobacillus rhamnosus LGG (MPN@L). These were compared with TA-based MPN@L to evaluate their effectiveness in alleviating IBD. All MPN@L complexes demonstrated superior adhesion and retention compared to uncoated probiotics in both ex vivo and in vivo models. Specifically, EGC@L exhibited the highest survival rate throughout gastrointestinal digestion, with a 2.7 log CFU/mL improvement over uncoated probiotics, and showed optimal retention in murine intestine with a fluorescence intensity of 24.3 × 106 p/s/cm2/sr by day four. All MPN@L formation effectively alleviated ulcerative colitis by reducing myeloperoxidase levels, modulating cytokines profiles, and enhancing gut microbiota. EGC@L particularly increased beneficial bacterial genera, including Lactobacillus, Adlercreutzia, and Oscillospira, while decreasing the pro-inflammatory genera. This study highlights the potential of MPN-based probiotic microencapsulation to enhanced treatment for gastrointestinal disorders, expending the application of probiotic microencapsulation in IBD therapy.
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Affiliation(s)
- Lu Gao
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Yunjian Liu
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Ling Ye
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Sizhi Liang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Jiancan Lin
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Jiaying Zeng
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Lei Lei
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Qiang Huang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health, Guangzhou, 510640, China
| | - Yujun Wan
- Department of Biochemistry, School of Biological Sciences, University of Cambridge, Cambridge, CB2 1QW, UK.
| | - Bin Zhang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China; Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health, Guangzhou, 510640, China.
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3
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Xie R, Fan D, Cheng X, Yin Y, Li H, Wegner SV, Chen F, Zeng W. Living therapeutics: Precision diagnosis and therapy with engineered bacteria. Biomaterials 2025; 321:123342. [PMID: 40252271 DOI: 10.1016/j.biomaterials.2025.123342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 04/02/2025] [Accepted: 04/12/2025] [Indexed: 04/21/2025]
Abstract
Bacteria-based therapy has emerged as a promising strategy for cancer treatment, offering the potential for targeted tumor delivery, immune activation, and modulation of the tumor microenvironment. However, the unpredictable behavior, safety concerns, and limited efficacy of wild-type bacteria pose significant challenges to their clinical translation. Recent advancements in synthetic biology and chemical engineering have enabled the development of precisely engineered bacterial platforms with enhanced controllability, targeted delivery, and reduced toxicity. This review summarize the current progress of engineered bacteria in cancer therapy. We first introduce the theoretical underpinnings and key advantages of bacterial therapies in cancer. Subsequently, we delve into the applications of genetic engineering and chemical modification techniques to enhance their therapeutic potential. Finally, we address critical challenges and future prospects, with a focus on improving safety and efficacy. This review aims to stimulate further research and provide valuable insights into the development of engineered bacterial therapies for precision oncology.
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Affiliation(s)
- Ruyan Xie
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China
| | - Duoyang Fan
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China
| | - Xiang Cheng
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China
| | - Ying Yin
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China
| | - Haohan Li
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China
| | - Seraphine V Wegner
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, 48149, Germany
| | - Fei Chen
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China.
| | - Wenbin Zeng
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; Hunan Key Laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases, Changsha, 410078, China.
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4
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Li J, Chen W, Lu Z, Li H, Chi X, Ma X, Tang Y, Liu Y, Lin M, Liu Z. Nanoengineered Azotobacter Pseudomonas stutzeri A1501 for Soil Ecology Restoration and Biological Nitrogen Fixation. ACS NANO 2025. [PMID: 40343854 DOI: 10.1021/acsnano.4c15823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2025]
Abstract
Biological nitrogen fixation (BNF) facilitated by nitrogen-fixing bacteria (NFBac) offers a sustainable alternative to conventional nitrogen fertilizers. However, acidic soil conditions, characterized by reduced pH levels, nutrient deficiencies, and disrupted microbiomes, present a significant challenge to the effectiveness of NFBac. This study proposes a nanoengineering approach to bolster the resilience and functionality of NFBac in acidic soils. Azotobacter Pseudomonas stutzeri A1501 cells are sequentially coated with a pH-responsive copolymer L100-55 and calcium phosphate nanoparticles (CaP NPs), resulting in the development of a robust biofertilizer (A1501@L@CaP). This biofertilizer can effectively buffer acidic pH levels, release nutrients, promote nutrient cycling, enhance soil enzymatic activity, and modulate soil microbiomes, rendering substantial enhancements in soil ecology and plant growth. The engineered NFBac offer a viable strategy for integrating BNF into acidic soils in a sustainable manner.
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Affiliation(s)
- Juanjuan Li
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Wenxin Chen
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Zhenzhang Lu
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Hong Li
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Xue Chi
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Xiang Ma
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Yanqiong Tang
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
| | - Yong Liu
- School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China
| | - Min Lin
- College of Agriculture, Henan University, Kaifeng 475001, China
| | - Zhu Liu
- School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, Haikou, Hainan 570228, China
- Faculty of Animal Science and Technology, Key Laboratory of Animal Nutrition and Feed Science of Yunnan Province, Yunnan Agricultural University, Kunming 650201, China
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5
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Zhong H, Jiang J, Hussain M, Zhang H, Chen L, Guan R. The Encapsulation Strategies for Targeted Delivery of Probiotics in Preventing and Treating Colorectal Cancer: A Review. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2500304. [PMID: 40192333 DOI: 10.1002/advs.202500304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 03/01/2025] [Indexed: 05/16/2025]
Abstract
Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. It is associated with imbalanced gut microbiota. Probiotics can help restore this balance, potentially reducing the risk of CRC. However, the hostile environment and constant changes in the gastrointestinal tract pose significant challenges to the efficient delivery of probiotics to the colon. Traditional delivery methods are often insufficient due to their low viability and lack of targeting. To address these challenges, researchers are increasingly focusing on innovative encapsulation technologies. One such approach is single-cell encapsulation, which involves applying nanocoatings to individual probiotic cells. This technique can improve their resistance to the harsh gastrointestinal environment, enhance mucosal adhesion, and facilitate targeted release, thereby increasing the effectiveness of probiotic delivery. This article reviews the latest developments in probiotic encapsulation methods for targeted CRC treatment, emphasizing the potential benefits of emerging single-cell encapsulation techniques. It also analyzes and compares the advantages and disadvantages of current encapsulation technologies. Furthermore, it elucidates the underlying mechanisms through which probiotics can prevent and treat CRC, evaluates the efficacy and safety of probiotics in CRC treatment and adjuvant therapy, and discusses future directions and potential challenges in the targeted delivery of probiotics for CRC treatment and prevention.
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Affiliation(s)
- Hao Zhong
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, 310014, China
| | - Jin Jiang
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, 310014, China
| | - Muhammad Hussain
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, 310014, China
- Moganshan Institute ZJUT, Kangqian, Deqing, 313200, China
| | - Haoxuan Zhang
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, 310014, China
| | - Ling Chen
- Sanya Branch of Hainan Academy of Inspection and Testing, San Ya, 572011, China
| | - Rongfa Guan
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, 310014, China
- Moganshan Institute ZJUT, Kangqian, Deqing, 313200, China
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6
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Zhang JP, Li ML, Ren DL, Yang QL, Mao J, Liu SP. High-throughput screening of probiotics in fermented foods and their potential application in alleviating alcohol-induced damage. Food Funct 2025; 16:2564-2576. [PMID: 40035662 DOI: 10.1039/d4fo05735j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
This study is dedicated to screening strains with high ethanol degradation capabilities from various fermented products, aiming to mitigate the adverse health effects of alcohol consumption. The research began with the isolation of target strains from pickled vegetables, sauerkraut, enzymes, and spoiled yellow wine, and then established a high-throughput screening method based on the color reaction of WST-8 and NADH. By utilizing automated liquid handling and imaging technologies, rapid transfer and cultivation of single colonies, as well as efficient assessment of ethanol degradation activity, were achieved. The selected strains were rescreened, and their ethanol tolerance, and the ability to degrade ethanol and acetaldehyde were comprehensively evaluated. Ultimately, the potential protective effects of the target strains against alcoholic liver injury were assessed through animal experiments. The study successfully constructed a high-throughput screening platform, providing an effective technical strategy for the rapid identification and evaluation of strains capable of degrading ethanol.
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Affiliation(s)
- Jun-Pu Zhang
- School of Food Science and Technology, Jiangnan university, Wuxi, Jiangsu 214122, China.
- National Engineering Research Centre of Cereal Fermentation and Food Biomanufacturing, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Ming-Liang Li
- School of Food Science and Technology, Jiangnan university, Wuxi, Jiangsu 214122, China.
- National Engineering Research Centre of Cereal Fermentation and Food Biomanufacturing, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Dong-Liang Ren
- School of Food Science and Technology, Jiangnan university, Wuxi, Jiangsu 214122, China.
- National Engineering Research Centre of Cereal Fermentation and Food Biomanufacturing, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Qi-Lin Yang
- School of Food Science and Technology, Jiangnan university, Wuxi, Jiangsu 214122, China.
- National Engineering Research Centre of Cereal Fermentation and Food Biomanufacturing, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Jian Mao
- School of Food Science and Technology, Jiangnan university, Wuxi, Jiangsu 214122, China.
- National Engineering Research Centre of Cereal Fermentation and Food Biomanufacturing, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- Shaoxing Key Laboratory of Traditional Fermentation Food and Human Health, Jiangnan University (Shaoxing) Industrial Technology Research Institute, Shaoxing, Zhejiang 312000, China
| | - Shuang-Ping Liu
- School of Food Science and Technology, Jiangnan university, Wuxi, Jiangsu 214122, China.
- National Engineering Research Centre of Cereal Fermentation and Food Biomanufacturing, State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
- Shaoxing Key Laboratory of Traditional Fermentation Food and Human Health, Jiangnan University (Shaoxing) Industrial Technology Research Institute, Shaoxing, Zhejiang 312000, China
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7
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Wu J, Ye W, Yu J, Zhou T, Zhou N, K P Ng D, Li Z. Engineered bacteria and bacterial derivatives as advanced therapeutics for inflammatory bowel disease. Essays Biochem 2025; 69:EBC20253003. [PMID: 40014418 DOI: 10.1042/ebc20253003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 01/29/2025] [Indexed: 03/01/2025]
Abstract
Inflammatory bowel disease (IBD), a chronic and relapsing-remitting condition, is inadequately managed by conventional therapies that often lack targeting specificity and carry significant side effects, particularly failing to address intestinal barrier repair and microbial balance. Probiotics, with their strong colonization capabilities, present a novel approach to drug delivery. Various engineering strategies have been developed to enhance the targeting ability of probiotics to inflammation sites, enabling precise delivery or in situ synthesis of therapeutic molecules to expand their multifunctional potential. This review discusses the recent advancements in bacterial modifications, including surface physico-chemical and biological coating, genetic engineering, outer membrane vesicles, minicells, and bacterial ghosts, all of which can enhance therapeutic localization. We also outline critical preclinical considerations, such as delivery frequency, systemic distribution, immune evasion, and gene contamination risks, for clinical translation. These engineered bacteria and bacterial derivatives hold great promise for personalized and sustained IBD treatments, providing a new frontier for therapy tailored to the complex inflammatory environment of IBD.
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Affiliation(s)
- Jingyuan Wu
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China
| | - Wanlin Ye
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China
| | - Jie Yu
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, P. R. China
| | - Tuoyu Zhou
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China
- The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Guangdong, 518172, P. R. China
| | - Nuo Zhou
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China
| | - Dennis K P Ng
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong, P. R. China
| | - Zhaoting Li
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, P. R. China
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8
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Zahedifard Z, Mahmoodi S, Ghasemian A. Genetically Engineered Bacteria as a Promising Therapeutic Strategy Against Cancer: A Comprehensive Review. Biotechnol Appl Biochem 2025. [PMID: 39985148 DOI: 10.1002/bab.2738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 02/06/2025] [Indexed: 02/24/2025]
Abstract
As a significant cause of global mortality, the cancer has also economic impacts. In the era of cancer therapy, mitigating side effects and costs and overcoming drug resistance is crucial. Microbial species can grow inside the tumor microenvironment and inhibit cancer growth through direct killing of tumor cells and immunoregulatory effects. Although microbiota or their products have demonstrated anticancer effects, the possibility of acting as pathogens and exerting side effects in certain individuals is a risk. Hence, several genetically modified/engineered bacteria (GEB) have been developed to this aim with ability of diagnosing and selective targeting and destruction of cancers. Additionally, GEB are expected to be considerably more efficient, safer, more permeable, less costly, and less invasive theranostic approaches compared to wild types. Potential GEB strains such as Escherichia coli (Nissle 1917, and MG1655), Salmonella typhimurium YB1 SL7207 (aroA gene deletion), VNP20009 (∆msbB/∆purI) and ΔppGpp (PTet and PBAD), and Listeria monocytogenes Lmat-LLO have been developed to combat cancer cells. When used in tandem with conventional treatments, GEB substantially improve the efficacy of anticancer therapy outcomes. In addition, public acceptance, optimal timing (s), duration (s), dose (s), and strains identification, interactions with other strains and the host cells, efficacy, safety and quality, and potential risks and ethical dilemmas include major challenges.
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Affiliation(s)
- Zahra Zahedifard
- Department of Medical Biotechnology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Shirin Mahmoodi
- Department of Medical Biotechnology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Abdolmajid Ghasemian
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
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9
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Pan C, Jiang X, Wei J, Liu C, Zhang M, Gao C, Chen R, Yang C, Wang B, Yu M, Gan Y. Ameba-inspired strategy enhances probiotic efficacy via prebound nutrient supply. Nat Commun 2025; 16:1827. [PMID: 39979278 PMCID: PMC11842784 DOI: 10.1038/s41467-025-57071-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 02/11/2025] [Indexed: 02/22/2025] Open
Abstract
Nutrient competition with indigenous microbes or pathogens presents a significant challenge for oral probiotic efficacy. To address this issue, we develop an ameba-inspired food-carrying strategy (AIFS) by prebinding ginger-derived exosome-like nanoparticles (GELNs) onto probiotics as food depots. AIFS enables probiotics to efficiently and exclusively consume GELNs in situ, even in the presence of competing bacteria. This results in up to 21 times higher uptake efficiency compared to unengineered probiotics, dramatically accelerating probiotic proliferation. Meanwhile, AIFS potentiates probiotics' resistance to multiple GI stressors. In a murine model of colitis, AIFS can improve the abundance of probiotics and inhibit pathogens, maintaining intestinal flora homeostasis. Additionally, it can upregulate the anti-inflammatory IL-10, reduce the proinflammatory IL-1β, and repair damaged intestinal mucus. Thereby, AIFS displays potently elevated prophylactic and therapeutic efficacy for colitis mice. This work provides a method for microbial engineering, with broad implications for microbiotherapy and gut health.
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Affiliation(s)
- Chao Pan
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- University of Chinese Academy of Sciences, Beijing, PR China
| | - Xiuxian Jiang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- University of Chinese Academy of Sciences, Beijing, PR China
| | - Junchao Wei
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- School of Pharmacy, Henan University, Kaifeng, PR China
| | - Chang Liu
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- University of Chinese Academy of Sciences, Beijing, PR China
| | - Min Zhang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- University of Chinese Academy of Sciences, Beijing, PR China
| | - Chuan Gao
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Rongrong Chen
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Canyu Yang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China
| | - Bingqi Wang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- University of Chinese Academy of Sciences, Beijing, PR China
| | - Miaorong Yu
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China
- University of Chinese Academy of Sciences, Beijing, PR China
| | - Yong Gan
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
- University of Chinese Academy of Sciences, Beijing, PR China.
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
- NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing, PR China.
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10
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Zhang X, Zang Z, Liang Z, Xu X, Zheng J, Liang N, Shabiti S, Wang Z, Yu S, Wang Y, Liu C, Li W, Cai L. Nanobiohybrid Oncolytic Bacteria with Optimized Intratumoral Distribution for Combined Sono-Photodynamic/Immunotherapy. ACS NANO 2025; 19:6437-6453. [PMID: 39902865 DOI: 10.1021/acsnano.4c16740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
"Living therapeutic carriers" present a promising avenue for cancer research, but it is still challenging to achieve uniform and durable distribution of payloads throughout the solid tumor owing to the tumor microenvironment heterogeneity. Herein, a living drug sprinkle biohybrid (YB1-HCNs) was constructed by hitching acid/enzyme-triggered detachable nanoparticles (HCNs) backpack on the surface of metabolic oligosaccharide-engineered oncolytic bacteria YB1. Along with the process of tumor penetration by bacterial hypoxia navigation, YB1-HCNs responsively and continuously release HCNs, achieving a uniform distribution of loaded agents throughout the tumor. Upon successive irradiation of laser and ultrasound (US), the HCNs can separately generate type II and type I ROS for superior sono-photodynamic therapy (SPDT), which enables HCNs to synergize with YB1 for a satisfactory therapeutic effect in both superficial normoxic and deep hypoxic regions of the tumor. After a single dose, this efficient combination realized 98.3% primary tumor inhibition rate and prolonged survival of mice for 90 days with no recurrence, further inducing a powerful immunological memory effect to completely suppress tumor rechallenge in cured mice. Such a bacterial hybridization vector enables optimization of the spatial distribution of YB1 and HCNs, providing an innovative strategy to maximize therapeutic outcomes and evoke durable antitumor immunity.
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Affiliation(s)
- Xu Zhang
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Zhongsheng Zang
- Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Zhenguo Liang
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Xiaoyu Xu
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Jinling Zheng
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Na Liang
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Shayibai Shabiti
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Zixi Wang
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Shiwen Yu
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Yujue Wang
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
| | - Chenli Liu
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
- Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Wenjun Li
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Lintao Cai
- Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, CAS Key Laboratory of Biomedical Imaging Science and System, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen 518055, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
- Sino-Euro Center of Biomedicine and Health, Luohu, Shenzhen, 518024, P. R. China
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Zhang Y, Zhang X, Lv L, Gao S, Li X, Wang R, Wang P, Shi F, She J, Wang Y. Versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex with prolonged intestinal retention for synergistic therapy of inflammatory bowel disease. Carbohydr Polym 2025; 350:123063. [PMID: 39647933 DOI: 10.1016/j.carbpol.2024.123063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/31/2024] [Accepted: 11/23/2024] [Indexed: 12/10/2024]
Abstract
To achieve effective long-term synergistic treatment of inflammatory bowel disease (IBD) with probiotics, we developed a versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex. Inulin/TFA/SS nanoparticles were fabricated by inulin, trans-ferulic acid (TFA), and silk sericin (SS), and then loaded onto the surface of poly-l-lysine (PLL) and poly-glutamic acid (PGA)-coated Bifidobacterium longum (BL) to obtain BL@PLL-PGA-Inulin/TFA/SS NPs (BL@PP-NPs). This design simultaneously endowed the complex with excellent gastrointestinal resistance, antioxidant, and anti-inflammation abilities. Moreover, the inulin in the nanoparticles acts as a prebiotic, promoting the Bifidobacterium's rapid proliferation to exert effects within a short period. Compared with uncoated BL, BL@PP-NPs exhibited excellent gastric acid tolerance and up to 31.32-fold colonic colonization, and the ROS scavenging and proliferative capacity were increased by 5.61- and 1.39-fold, respectively. In a mouse model of dextran sulfate sodium (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, the components of Inulin/TFA/SS NPs synergized with probiotics to efficiently treat IBD by attenuating oxidative stress, decreasing inflammation, repairing intestinal barrier, and promoting the rapid proliferation of probiotics to reverse gut microbial disorders. Collectively, food-grade BL@PP-NPs represent a novel approach to probiotic modification that offers an effective, safe, and synergistic therapy for IBD.
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Affiliation(s)
- Yujie Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Xiaojiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Lianxi Lv
- Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Sheng Gao
- Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Xiang Li
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China; Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Ruochen Wang
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Pengqian Wang
- Department of Chemical Engineering, School of Water and Environment, Chang'an University, 710064 Xi'an, Shaanxi, PR China.
| | - Feiyu Shi
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
| | - Ya Wang
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
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12
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Gao S, Li X, Han B. Bacterial and bacterial derivatives-based drug delivery systems: a novel approach for treating central nervous system disorders. Expert Opin Drug Deliv 2025; 22:163-180. [PMID: 39688950 DOI: 10.1080/17425247.2024.2444364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 12/13/2024] [Accepted: 12/16/2024] [Indexed: 12/19/2024]
Abstract
INTRODUCTION Bacteria and their derivatives show great potential as drug delivery systems due to their unique chemotaxis, biocompatibility, and targeting abilities. In CNS disease treatment, bacterial carriers can cross the blood-brain barrier (BBB) and deliver drugs precisely, overcoming limitations of traditional methods. Advances in genetic engineering, synthetic biology, and nanotechnology have transformed these systems into multifunctional platforms for personalized CNS treatment. AREAS COVERED This review examines the latest research on bacterial carriers for treating ischemic brain injury, neurodegenerative diseases, and gliomas. Bacteria efficiently cross the blood-brain barrier via active targeting, endocytosis, paracellular transport, and the nose-to-brain route for precise drug delivery. Various bacterial drug delivery systems, such as OMVs and bacterial ghosts, are explored for their design and application. Databases were searched in Google Scholar for the period up to December 2024. EXPERT OPINION Future developments in bacterial drug delivery will rely on AI-driven design and high-throughput engineering, enhancing treatment precision. Personalized medicine will further optimize bacterial carriers for individual patients, but challenges such as biosafety, immune rejection, and scalability must be addressed. As multimodal diagnostic and therapeutic strategies advance, bacterial carriers are expected to play a central role in CNS disease treatment, offering novel precision medicine solutions.
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Affiliation(s)
- Shizhu Gao
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, PR China
| | - Xin Li
- Orthopedic Medical Center, 2nd hospital of Jilin University, Changchun, PR China
| | - Bing Han
- Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, PR China
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13
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Chen A, Gong Y, Wu S, Du Y, Liu Z, Jiang Y, Li J, Miao YB. Navigating a challenging path: precision disease treatment with tailored oral nano-armor-probiotics. J Nanobiotechnology 2025; 23:72. [PMID: 39893419 PMCID: PMC11786591 DOI: 10.1186/s12951-025-03141-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/19/2025] [Indexed: 02/04/2025] Open
Abstract
Oral probiotics have significant potential for preventing and treating many diseases. Yet, their efficacy is often hindered by challenges related to survival and colonization within the gastrointestinal tract. Nanoparticles emerge as a transformative solution, offering robust protection and enhancing the stability and bioavailability of these probiotics. This review explores the innovative application of nanoparticle-armored engineered probiotics for precise disease treatment, specifically addressing the physiological barriers associated with oral administration. A comprehensive evaluation of various nano-armor probiotics and encapsulation methods is provided, carefully analyzing their respective merits and limitations, alongside strategies to enhance probiotic survival and achieve targeted delivery and colonization within the gastrointestinal tract. Furthermore, the review explores the potential clinical applications of nano-armored probiotics in precision therapeutics, critically addressing safety and regulatory considerations, and proposing the innovative concept of 'probiotic intestinal colonization with nano armor' for brain-targeted therapies. Ultimately, this review aspires to guide the advancement of nano-armored probiotic therapies, driving progress in precision medicine and paving the way for groundbreaking treatment modalities.
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Affiliation(s)
- Anmei Chen
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Ying Gong
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Shaoquan Wu
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Ye Du
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Zhijun Liu
- Urology Institute of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, 518000, China
| | - Yuhong Jiang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China.
| | - Jiahong Li
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China.
| | - Yang-Bao Miao
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China.
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Cao MX, Qian ZY, Liang YJ, Liu QY, Wang HP, Meng Y, Wang YS, Wang Y. Layer-by-layer coated probiotics with tannic acid-Ca 2+ and casein phosphopeptide complexes for caries prevention and enamel remineralization. iScience 2025; 28:111579. [PMID: 39811639 PMCID: PMC11732097 DOI: 10.1016/j.isci.2024.111579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/05/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025] Open
Abstract
Dental caries is a common disease resulting from tooth demineralization caused by bacterial plaque. Probiotics have shown great potential against caries by regulating the balance of oral flora. However, obstacles such as poor colonization and lysozyme sensitivity in oral cavity hinder their further application. In this study, an efficient layer-by-layer surface coating of tannic acid (TA)-Ca2+ and casein phosphopeptide (CPP) was applied to the probiotic Bifidobacterium infantis (BI) with potential anti-caries activity. Multi-functionalized probiotics thus prepared (called BI@TA-Ca2+@CPP) exhibited similar growth pattern, resistance to lysozyme and enhanced colonization potential. The ability of BI@TA-Ca2+@CPP in inhibiting cariogenic biofilm formation was improved. Moreover, BI@TA-Ca2+@CPP showed excellent remineralization efficacy. In a caries-induced rat model, BI@TA-Ca2+@CPP significantly prevented the occurrence and progression of tooth decay, meanwhile showing good biocompatibility. In summary, this study underlines the importance of probiotics coating in antibiofilm and remineralization activity as a promising strategy against dental caries.
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Affiliation(s)
- Ming-Xin Cao
- Department of Orthodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
- Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Zhan-Yin Qian
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Yan-Jie Liang
- Department of Orthodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
- Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Qi-Yao Liu
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Han-Ping Wang
- Department of Orthodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
- Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Yang Meng
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Yin-Song Wang
- Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
- The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
| | - Yue Wang
- Department of Orthodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
- Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, P.R. China
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15
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Pan Y, Pan C, Mao L, Yu P. Neuromodulation with chemicals: Opportunities and challenges. FUNDAMENTAL RESEARCH 2025; 5:55-62. [PMID: 40166084 PMCID: PMC11955035 DOI: 10.1016/j.fmre.2024.04.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/02/2025] Open
Abstract
Chemicals play a crucial role in neurophysiological and neuropathological processes. By regulating the concentration of specific chemicals, receptors on the neuron cell membrane can be modulated to activate or inhibit, thereby influencing specific ion channels and facilitating neuromodulation. This review introduces several chemical modulation techniques, such as microinjection, electrode/nanoparticle-based chemical delivery methods, in situ electrochemical synthesis and chemogenetics. While these techniques show promise in expanding the application of chemical neuromodulation, they currently exhibit different degrees of shortcomings and room for improvement. This review summarizes the opportunities and challenges for chemical neuromodulation methods and provide an outlook for their prospects in the future.
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Affiliation(s)
- Yifei Pan
- Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
| | - Cong Pan
- Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
| | - Lanqun Mao
- College of Chemistry, Beijing Normal University, Beijing 100875, China
| | - Ping Yu
- Key Laboratory of Analytical Chemistry for Living Biosystems Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
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16
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Zou ZP, Cai Z, Zhang XP, Zhang D, Xu CY, Zhou Y, Liu R, Ye BC. Delivery of Encapsulated Intelligent Engineered Probiotic for Inflammatory Bowel Disease Therapy. Adv Healthc Mater 2025; 14:e2403704. [PMID: 39629555 DOI: 10.1002/adhm.202403704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/21/2024] [Indexed: 01/29/2025]
Abstract
Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis. The MM delivery system features an external mucosal coating composed of hyaluronic acid and epigallocatechin gallate, along with internal microspheres of highly biocompatible polyserine modified alginates encapsulating with the engineered probiotics. The MM delivery system effectively protects engineered bacteria harsh environment in stomach and significantly improves intestinal adhesion of the probiotics, extending colonization up to 24 h, and does not affect the entry of biomarker or release of Avcystatin. It exhibits notable diagnostic and therapeutic efficacy in inflammatory bowel disease models, thus facilitating the advancement of live biotherapeutic products toward clinical application.
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Affiliation(s)
- Zhen-Ping Zou
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Zhihao Cai
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
- Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Key Laboratory of Specially Functional Polymeric Materials and Related Technology (Ministry of Education), Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Xiao-Peng Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Donghui Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Chu-Ying Xu
- Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China
| | - Ying Zhou
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Runhui Liu
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
- Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Key Laboratory of Specially Functional Polymeric Materials and Related Technology (Ministry of Education), Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China
| | - Bang-Ce Ye
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China
- Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China
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17
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Wang Q, Jin L, Yang H, Yu L, Cao X, Mao Z. Bacteria/Nanozyme Composites: New Therapeutics for Disease Treatment. SMALL METHODS 2025; 9:e2400610. [PMID: 38923867 DOI: 10.1002/smtd.202400610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 06/11/2024] [Indexed: 06/28/2024]
Abstract
Bacterial therapy is recognized as a cost-effective treatment for several diseases. However, its development is hindered by limited functionality, weak inherent therapeutic effects, and vulnerability to harsh microenvironmental conditions, leading to suboptimal treatment activity. Enhancing bacterial activity and therapeutic outcomes emerges as a pivotal challenge. Nanozymes have garnered significant attention due to their enzyme-mimic activities and high stability. They enable bacteria to mimic the functions of gene-edited bacteria expressing the same functional enzymes, thereby improving bacterial activity and therapeutic efficacy. This review delineates the therapeutic mechanisms of bacteria and nanozymes, followed by a summary of strategies for preparing bacteria/nanozyme composites. Additionally, the synergistic effects of such composites in biomedical applications such as gastrointestinal diseases and tumors are highlighted. Finally, the challenges of bacteria/nanozyme composites are discussed and propose potential solutions. This study aims to provide valuable insights to offer theoretical guidance for the advancement of nanomaterial-assisted bacterial therapy.
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Affiliation(s)
- Qirui Wang
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Lulu Jin
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Huang Yang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Lisha Yu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Xinran Cao
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Zhengwei Mao
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China
- State Key Laboratory of Transvascular Implantation Devices, Zhejiang, Hangzhou, 310009, China
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18
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Han Q, Yang F, Chen M, Zhang M, Wang L, Wang H, Liu J, Cao Z. Coating Dormant Collagenase-Producing Bacteria with Metal-Anesthetic Networks for Precision Tumor Therapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2407402. [PMID: 39291426 PMCID: PMC11558152 DOI: 10.1002/advs.202407402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/09/2024] [Indexed: 09/19/2024]
Abstract
Tumor malignancy highly depends on the stiffness of tumor matrix, which mainly consists of collagen. Despite the destruction of tumor matrix is conducive to tumor therapy, it causes the risk of tumor metastasis. Here, metal-anesthetic network-coated dormant collagenase-producing Clostridium is constructed to simultaneously destruct tumor matrix and inhibit tumor metastasis. By metal-phenolic complexation and π-π stacking interactions, a Fe3+-propofol network is formed on bacterial surface. Coated dormant Clostridium can selectively germinate and rapidly proliferate in tumor sites due to the ability of carried Fe3+ ions to promote bacterial multiplication. Intratumoral colonization of Clostridium produces sufficient collagenases to degrade tumor collagen mesh and the loaded propofol restrains tumor metastasis by inhibiting tumor cell migration and invasion. Meanwhile, the delivered Fe3+ ions are reduced to the Fe2+ form by intracellular glutathione, thereby inducing potent Fenton reaction to trigger lipid peroxidation and ultimate ferroptosis of tumor cells. In addition to a satisfactory safety, a single intratumoral injection of coated dormant Clostridium not only effectively retards the growth of established large primary tumors, but also significantly suppresses distal lung metastasis in two different orthotopic tumor models. This work proposes a strategy to develop advanced therapeutics for malignant tumor treatment and metastasis prevention.
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Affiliation(s)
- Qiuju Han
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
- School of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai200240China
| | - Fengmin Yang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
| | - Mian Chen
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
- School of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai200240China
| | - Mengmeng Zhang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
| | - Lu Wang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
| | - Hongxia Wang
- Department of Medical OncologyFudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai200032China
| | - Jinyao Liu
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
- School of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai200240China
| | - Zhenping Cao
- Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineInstitute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China
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19
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Gui Y, Sun Q, Li K, Lin L, Zhou H, Ma J, Li C. Bioinspired gelated cell sheet-supported lactobacillus biofilm for aerobic vaginitis diagnosis and treatment. SCIENCE ADVANCES 2024; 10:eadq2732. [PMID: 39485840 PMCID: PMC11529721 DOI: 10.1126/sciadv.adq2732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/30/2024] [Indexed: 11/03/2024]
Abstract
Aerobic vaginitis (AV) is a long-standing inflammatory disease that affects female patients. The use of antibiotics is a common means for AV treatment, but it will indiscriminately kill both pathogenic bacteria and beneficial strains, which easily causes vaginal dysbacteriosis and infection recurrence. Herein, we describe a bioinspired strategy for fabricating gelated cell sheet-supported lactobacillus biofilms (GCS-LBs) for AV treatment. Compared with common planktonic probiotic formulations, probiotic biofilms forming on a robust GCS exhibit enhanced stress tolerance and better colonization capacity in the mouse vagina. Moreover, DNA nanodevices are decorated on the GCS and dynamically report the microenvironment change of biofilms for timely evaluating bacterium activity, both in vitro and in vivo. Consequently, GCS-LBs are used for treating AV in an Escherichia coli-infected mouse model, which shows enhanced therapeutic efficacy compared with conventional antibiotic or lactobacillus monotherapy. Overall, the GCS-LB shows promise as a potent multifunctional tool to combat bacterial infection.
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Affiliation(s)
- Yueyue Gui
- Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P. R. China
| | - Qingfei Sun
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, P. R. China
| | - Kexin Li
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, P. R. China
| | - Longjia Lin
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, P. R. China
| | - Han Zhou
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, P. R. China
| | - Jiehua Ma
- Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P. R. China
| | - Chao Li
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, P. R. China
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20
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Xu C, Guo J, Chang B, Zhang Y, Tan Z, Tian Z, Duan X, Ma J, Jiang Z, Hou J. Design of probiotic delivery systems and their therapeutic effects on targeted tissues. J Control Release 2024; 375:20-46. [PMID: 39214316 DOI: 10.1016/j.jconrel.2024.08.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 08/14/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Abstract
The microbiota at different sites in the body is closely related to disease. The intake of probiotics is an effective strategy to alleviate diseases and be adjuvant in their treatment. However, probiotics may suffer from harsh environments and colonization resistance, making it difficult to maintain a sufficient number of live probiotics to reach the target sites and exert their original probiotic effects. Encapsulation of probiotics is an effective strategy. Therefore, probiotic delivery systems, as effective methods, have been continuously developed and innovated to ensure that probiotics are effectively delivered to the targeted site. In this review, initially, the design of probiotic delivery systems is reviewed from four aspects: probiotic characteristics, processing technologies, cell-derived wall materials, and interactions between wall materials. Subsequently, the review focuses on the effects of probiotic delivery systems that target four main microbial colonization sites: the oral cavity, skin, intestine, and vagina, as well as disease sites such as tumors. Finally, this review also discusses the safety concerns of probiotic delivery systems in the treatment of disease and the challenges and limitations of implementing this method in clinical studies. It is necessary to conduct more clinical studies to evaluate the effectiveness of different probiotic delivery systems in the treatment of diseases.
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Affiliation(s)
- Cong Xu
- College of Food Science and Engineering, Guiyang University, Guiyang 550005, China; Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China
| | - Jiahui Guo
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Baoyue Chang
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Yiming Zhang
- Department of Psychiatry and Mental Health, Dalian Medical University, Dalian 116044, China
| | - Zhongmei Tan
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Zihao Tian
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Xiaolei Duan
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China
| | - Jiage Ma
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China
| | - Zhanmei Jiang
- Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China.
| | - Juncai Hou
- College of Food Science and Engineering, Guiyang University, Guiyang 550005, China; Key Laboratory of Dairy Science, Northeast Agricultural University, College of Food Science, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Harbin 150028, China.
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21
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Lepori I, Roncetti M, Vitiello M, Barresi E, De Paolo R, Tentori PM, Baldanzi C, Santi M, Evangelista M, Signore G, Tedeschi L, Gravekamp C, Cardarelli F, Taliani S, Da Settimo F, Siegrist MS, Poliseno L. Enhancing the Anticancer Activity of Attenuated Listeria monocytogenes by Cell Wall Functionalization with "Clickable" Doxorubicin. ACS Chem Biol 2024; 19:2131-2140. [PMID: 39317359 PMCID: PMC11494506 DOI: 10.1021/acschembio.4c00250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/13/2024] [Accepted: 07/18/2024] [Indexed: 09/26/2024]
Abstract
Among bacteria used as anticancer vaccines, attenuated Listeria monocytogenes (Lmat) stands out, because it spreads from one infected cancer cell to the next, induces a strong adaptive immune response, and is suitable for repeated injection cycles. Here, we use click chemistry to functionalize the Lmat cell wall and turn the bacterium into an "intelligent carrier" of the chemotherapeutic drug doxorubicin. Doxorubicin-loaded Lmat retains most of its biological properties and, compared to the control fluorophore-functionalized bacteria, shows enhanced cytotoxicity against melanoma cells both in vitro and in a xenograft model in zebrafish. Our results show that drugs can be covalently loaded on the Lmat cell wall and pave the way to the development of new two-in-one therapeutic approaches combining immunotherapy with chemotherapy.
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Affiliation(s)
- Irene Lepori
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
- Oncogenomics
Unit, Core Research Laboratory, ISPRO, Pisa 56124, Italy
| | - Marta Roncetti
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
- Oncogenomics
Unit, Core Research Laboratory, ISPRO, Pisa 56124, Italy
- University
of Siena, Siena 53100, Italy
| | - Marianna Vitiello
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
- Oncogenomics
Unit, Core Research Laboratory, ISPRO, Pisa 56124, Italy
| | - Elisabetta Barresi
- Department
of Pharmacy, University of Pisa, Pisa 56126, Italy
- CISUP-Center
for Instrument Sharing, University of Pisa, Pisa 56126, Italy
| | - Raffaella De Paolo
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
- Oncogenomics
Unit, Core Research Laboratory, ISPRO, Pisa 56124, Italy
| | - Paolo Maria Tentori
- Center for
Nanotechnology Innovation @NEST, Istituto
Italiano di Tecnologia, Pisa 56126, Italy
| | - Caterina Baldanzi
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
- Oncogenomics
Unit, Core Research Laboratory, ISPRO, Pisa 56124, Italy
| | - Melissa Santi
- NEST-Scuola
Normale Superiore, Istituto Nanoscienze,
CNR (CNR-NANO), Pisa 56126, Italy
| | - Monica Evangelista
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
| | - Giovanni Signore
- Fondazione
Pisana per la Scienza ONLUS, San Giuliano Terme, Pisa 56017, Italy
| | - Lorena Tedeschi
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
| | - Claudia Gravekamp
- Department
of Microbiology and Immunology, Albert Einstein
College of Medicine, New York, New York 10461, United States
| | - Francesco Cardarelli
- NEST-Scuola
Normale Superiore, Istituto Nanoscienze,
CNR (CNR-NANO), Pisa 56126, Italy
| | - Sabrina Taliani
- Department
of Pharmacy, University of Pisa, Pisa 56126, Italy
- CISUP-Center
for Instrument Sharing, University of Pisa, Pisa 56126, Italy
| | - Federico Da Settimo
- Department
of Pharmacy, University of Pisa, Pisa 56126, Italy
- CISUP-Center
for Instrument Sharing, University of Pisa, Pisa 56126, Italy
| | - M. Sloan Siegrist
- Department
of Microbiology, University of Massachusetts, Amherst, Massachusetts 01003-9316, United
States
- Molecular
and Cellular Biology Graduate Program, University
of Massachusetts, Amherst, Massachusetts 01003-9316, United States
| | - Laura Poliseno
- Institute
of Clinical Physiology, National Research Council (CNR-IFC), Pisa 56124, Italy
- Oncogenomics
Unit, Core Research Laboratory, ISPRO, Pisa 56124, Italy
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22
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Yin X, Shan J, Dou L, Cheng Y, Liu S, Hassan RY, Wang Y, Wang J, Zhang D. Multiple bacteria recognition mechanisms and their applications. Coord Chem Rev 2024; 517:216025. [DOI: 10.1016/j.ccr.2024.216025] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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23
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Zhang Y, Wang Y, Zhang X, Wang P, Shi F, Zhang Z, Wang R, Wu D, She J. Gastrointestinal Self-Adaptive and Nutrient Self-Sufficient Akkermansia muciniphila-Gelatin Porous Microgels for Synergistic Therapy of Ulcerative Colitis. ACS NANO 2024; 18:26807-26827. [PMID: 39301762 DOI: 10.1021/acsnano.4c07658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
To realize effective and long-term synergistic therapy of ulcerative colitis (UC) with probiotics, we developed gastrointestinal self-adaptive and nutrient self-sufficient Akkermansia muciniphila (AKK)-gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs, AKK was covered with sequential layers of proanthocyanidins (PAs), mucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC (AKK@PMP), and then encapsulated within the methacrylate-modified gelatin porous microgels. AKK@GPMGs provide sufficient mucus as a nutrition source for AKK and boost resistance to stomach acid by 30.49-fold, and colonization in the intestines is enhanced by 83.46 times. The microgels can be dissociated by matrix metalloproteinase at the inflammatory sites of the intestine, and release AKK@PMP, which acts as "band-aid" that adheres to the inflamed colon for a long time and offers improved synergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase reactive oxygen species scavenging capacity by 26.47 times, improve the intestinal mucus layer thickness by 5.63 times, increase the goblet cells abundance by 3.93 times, reduce intestinal permeability by 5.60 times and significantly enhance beneficial gut microbiota while repressing harmful microbiota. These results indicate that AKK@GPMGs can restore mucus layer and tight junction integrity, reduce inflammation and oxidative stress, and regulate gut microbiota homeostasis to effectively treat intestinal inflammation.
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Affiliation(s)
- Yujie Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, P.R. China
| | - Ya Wang
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China
| | - Xiaojiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, P.R. China
| | - Pengqian Wang
- Department of Chemical Engineering, School of Water and Environment, Chang'an University, Xi'an 710064, P.R. China
| | - Feiyu Shi
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, P.R. China
| | - Zhe Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, P.R. China
| | - Ruochen Wang
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China
| | - Daocheng Wu
- Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P.R. China
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, P.R. China
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China
- Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China
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24
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Zhao R, Yu T, Li J, Niu R, Liu D, Wang W. Single-cell encapsulation systems for probiotic delivery: Armor probiotics. Adv Colloid Interface Sci 2024; 332:103270. [PMID: 39142064 DOI: 10.1016/j.cis.2024.103270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 05/28/2024] [Accepted: 08/03/2024] [Indexed: 08/16/2024]
Abstract
Functional foods or drugs based on probiotics have gained unprecedented attention and development due to the increasingly clear relationship between probiotics and human health. Probiotics can regulate intestinal microbiota, dynamically participating in various physiological activities to directly affect human health. Some probiotic-based functional preparations have shown great potential in treating multiple refractory diseases. Currently, the survival and activity of probiotic cells in complex environments in vitro and in vivo have taken priority, and various encapsulation systems based on food-derived materials have been designed and constructed to protect and deliver probiotics. However, traditional encapsulation technology cannot achieve precise protection for a single probiotic, which makes it unable to have a significant effect after release. In this case, single-cell encapsulation systems can be assembled based on biological interfaces to protect and functionalize individual probiotic cells, maximizing their physiological activity. This review discussed the arduous challenges of probiotics in food processing, storage, human digestion, and the commonly used probiotic encapsulation system. Besides, a novel technology of probiotic encapsulation was introduced based on single-cell coating, namely, "armor probiotics". We focused on the classification, structural design, and functional characteristics of armor coatings, and emphasized the essential functional characteristics of armor probiotics in human health regulation, including regulating intestinal health and targeted bioimaging and treatment of diseased tissues. Subsequently, the benefits, limitations, potential challenges, as well as future direction of armor probiotics were put forward. We hope this review may provide new insights and ideas for developing a single-cell probiotics encapsulating system.
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Affiliation(s)
- Runan Zhao
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China
| | - Ting Yu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China
| | - Jiaheng Li
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China; Innovation Center of Yangtze River Delta, Zhejiang University, Jiashan 314100, China
| | - Ruihao Niu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China
| | - Donghong Liu
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China; Innovation Center of Yangtze River Delta, Zhejiang University, Jiashan 314100, China; Ningbo Research Institute, Zhejiang University, Ningbo 315100, China
| | - Wenjun Wang
- College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Laboratory of Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China; Innovation Center of Yangtze River Delta, Zhejiang University, Jiashan 314100, China.
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25
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Wu L, Li L, Qiao L, Li C, Zhang S, Yin X, Du Z, Sun Y, Qiu J, Chang X, Wang B, Hua Z. Programmable Bacteria with Dynamic Virulence Modulation System for Precision Antitumor Immunity. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2404069. [PMID: 39058336 PMCID: PMC11423194 DOI: 10.1002/advs.202404069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 07/11/2024] [Indexed: 07/28/2024]
Abstract
Engineered bacteria-mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off-target bacterial toxicity narrows the therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors for safer antitumor applications. In this study, a genetically encoded microbial activation strategy is reported that uses tunable and dynamic expression of surface extracellular polysaccharides to improve bacterial biocompatibility while retaining therapeutic efficacy. Based on screening of genes associated with Salmonella survival in macrophages, a novel attenuated Salmonella chassis strain AIS (htrA gene-deficient) highly enriched in tumors after administration and rapidly cleared from normal organs are reported. Subsequently, an engineered bacterial strain, AISI-H, is constructed based on the AIS strain and an optimized quorum-sensing regulatory system. The AISI-H strain can achieve recovery of dynamic tumor-specific bacterial virulence through a novel HTRA-RCSA axis-based and quorum-sensing synthetic gene circuit-mediated increase in extracellular polysaccharide content. These strains act "off" in normal organs to avoid unwanted immune activation and "on" in tumors for precise tumor suppression in mice. The AISI-H strain shows significant tumor inhibition and potent activation of anticancer immunity in a melanoma mouse model. The AISI-H strain exhibits excellent biocompatibility. This bacterial regulation strategy expands the applications of microbe-based antitumor therapeutics.
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Affiliation(s)
- Leyang Wu
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
- Nanjing Generecom Biotechnology Co., Ltd., Nanjing, Jiangsu, 210023, P. R. China
- Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories, Inc., Changzhou, Jiangsu, 213164, P. R. China
| | - Lin Li
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Liyuan Qiao
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Chenyang Li
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Shuhui Zhang
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Xingpeng Yin
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Zengzheng Du
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Ying Sun
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Jiahui Qiu
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Xiaoyao Chang
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Bohao Wang
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
| | - Zichun Hua
- Department of Neurology of Nanjing Drum Tower Hospital and The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu, 21008, P. R. China
- Nanjing Generecom Biotechnology Co., Ltd., Nanjing, Jiangsu, 210023, P. R. China
- Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories, Inc., Changzhou, Jiangsu, 213164, P. R. China
- Faculty of Pharmaceutical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453002, P. R. China
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26
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Li M, Wang L, Lin D, Liu Z, Wang H, Yang Y, Sun C, Ye J, Liu Y. Advanced Bioinspired Multifunctional Platforms Focusing on Gut Microbiota Regulation. ACS NANO 2024; 18:20886-20933. [PMID: 39080827 DOI: 10.1021/acsnano.4c05013] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
Gut microbiota plays a crucial role in maintaining host homeostasis, impacting the progression and therapeutic outcomes of diseases, including inflammatory bowel disease, cancer, hepatic conditions, obesity, cardiovascular pathologies, and neurologic disorders, via immune, neural, and metabolic mechanisms. Hence, the gut microbiota is a promising target for disease therapy. The safety and precision of traditional microbiota regulation methods remain a challenge, which limits their widespread clinical application. This limitation has catalyzed a shift toward the development of multifunctional delivery systems that are predicated on microbiota modulation. Guided by bioinspired strategies, an extensive variety of naturally occurring materials and mechanisms have been emulated and harnessed for the construction of platforms aimed at the monitoring and modulation of gut microbiota. This review outlines the strategies and advantages of utilizing bioinspired principles in the design of gut microbiota intervention systems based on traditional regulation methods. Representative studies on the development of bioinspired therapeutic platforms are summarized, which are based on gut microbiota modulation to confer multiple pharmacological benefits for the synergistic management of diseases. The prospective avenues and inherent challenges associated with the adoption of bioinspired strategies in the refinement of gut microbiota modulation platforms are proposed to augment the efficacy of disease treatment.
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Affiliation(s)
- Muqing Li
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - LuLu Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - Demin Lin
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - Zihan Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - Hongliang Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - Yanfang Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - Chunmeng Sun
- Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China
| | - Jun Ye
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
| | - Yuling Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
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27
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Li C, Wang ZX, Xiao H, Wu FG. Intestinal Delivery of Probiotics: Materials, Strategies, and Applications. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2310174. [PMID: 38245861 DOI: 10.1002/adma.202310174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 01/04/2024] [Indexed: 01/22/2024]
Abstract
Probiotics with diverse and crucial properties and functions have attracted broad interest from many researchers, who adopt intestinal delivery of probiotics to modulate the gut microbiota. However, the major problems faced for the therapeutic applications of probiotics are the viability and colonization of probiotics during their processing, oral intake, and subsequent delivery to the gut. The challenges of simple oral delivery (stability, controllability, targeting, etc.) have greatly limited the use of probiotics in clinical therapies. Nanotechnology can endow the probiotics to be delivered to the intestine with improved survival rate and increased resistance to the adverse environment. Additionally, the progress in synthetic biology has created new opportunities for efficiently and purposefully designing and manipulating the probiotics. In this article, a brief overview of the types of probiotics for intestinal delivery, the current progress of different probiotic encapsulation strategies, including the chemical, physical, and genetic strategies and their combinations, and the emerging single-cell encapsulation strategies using nanocoating methods, is presented. The action mechanisms of probiotics that are responsible for eliciting beneficial effects are also briefly discussed. Finally, the therapeutic applications of engineered probiotics are discussed, and the future trends toward developing engineered probiotics with advanced features and improved health benefits are proposed.
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Affiliation(s)
- Chengcheng Li
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center for Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, China
| | - Zi-Xi Wang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Huining Xiao
- Department of Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, E3B 5A3, Canada
| | - Fu-Gen Wu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
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Lin X, Jiao R, Cui H, Yan X, Zhang K. Physiochemically and Genetically Engineered Bacteria: Instructive Design Principles and Diverse Applications. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2403156. [PMID: 38864372 PMCID: PMC11321697 DOI: 10.1002/advs.202403156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/18/2024] [Indexed: 06/13/2024]
Abstract
With the comprehensive understanding of microorganisms and the rapid advances of physiochemical engineering and bioengineering technologies, scientists are advancing rationally-engineered bacteria as emerging drugs for treating various diseases in clinical disease management. Engineered bacteria specifically refer to advanced physiochemical or genetic technologies in combination with cutting edge nanotechnology or physical technologies, which have been validated to play significant roles in lysing tumors, regulating immunity, influencing the metabolic pathways, etc. However, there has no specific reviews that concurrently cover physiochemically- and genetically-engineered bacteria and their derivatives yet, let alone their distinctive design principles and various functions and applications. Herein, the applications of physiochemically and genetically-engineered bacteria, and classify and discuss significant breakthroughs with an emphasis on their specific design principles and engineering methods objective to different specific uses and diseases beyond cancer is described. The combined strategies for developing in vivo biotherapeutic agents based on these physiochemically- and genetically-engineered bacteria or bacterial derivatives, and elucidated how they repress cancer and other diseases is also underlined. Additionally, the challenges faced by clinical translation and the future development directions are discussed. This review is expected to provide an overall impression on physiochemically- and genetically-engineered bacteria and enlighten more researchers.
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Affiliation(s)
- Xia Lin
- Central Laboratory and Department of UltrasoundSichuan Academy of Medical SciencesSichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo. 32, West Second Section, First Ring RoadChengduSichuan610072China
| | - Rong Jiao
- Central Laboratory and Department of UltrasoundSichuan Academy of Medical SciencesSichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo. 32, West Second Section, First Ring RoadChengduSichuan610072China
| | - Haowen Cui
- Central Laboratory and Department of UltrasoundSichuan Academy of Medical SciencesSichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo. 32, West Second Section, First Ring RoadChengduSichuan610072China
| | - Xuebing Yan
- Department of OncologyAffiliated Hospital of Yangzhou University. No.368Hanjiang Road, Hanjiang DistrictYangzhouJiangsu Province225012China
| | - Kun Zhang
- Central Laboratory and Department of UltrasoundSichuan Academy of Medical SciencesSichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo. 32, West Second Section, First Ring RoadChengduSichuan610072China
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Xu X, Zhong J, Su B, Xu L, Hong X, Lin J. Single-cell enzymatic cascade synthesis of testolactone enabled by engineering of polycyclic ketone monooxygenase and multi-gene expression fine-tuning. Int J Biol Macromol 2024; 275:133229. [PMID: 38897507 DOI: 10.1016/j.ijbiomac.2024.133229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 06/14/2024] [Accepted: 06/15/2024] [Indexed: 06/21/2024]
Abstract
The synthesis of steroids is challenging through multistep steroidal core modifications with high site-selectivity and productivity. In this work, a novel enzymatic cascade system was constructed for synthesis of testolactone by specific C17 lactonization/Δ1-dehydrogenation from inexpensive androstenedione using an engineered polycyclic ketone monooxygenase (PockeMO) and an appropriate 3-ketosteroid-Δ1-dehydrogenase (ReKstD). The focused saturation mutagenesis in the substrate binding pocket was implemented for evolution of PockeMO to eliminate the bottleneck effect. A best mutant MU3 (I225L/L226V/L532Y) was obtained with 20-fold higher specific activity compared to PockeMO. The catalytic efficiency (kcat/Km) of MU3 was 171-fold higher and the substrate scope shifted to polycyclic ketones. Molecular dynamic simulations suggested that the activity was improved by stabilization of the pre-lactonization state and generation of productive orientation of 4-AD mediated by distal L532Y mutation. Based on that, the three genes, MU3, ReKstD and a ketoreductase for NADPH regeneration, were rationally integrated in one cell via expression fine-tuning to form the efficient single cell catalyst E. coli S9. The single whole-cell biocatalytic process was scaled up and could generate 9.0 g/L testolactone with the high space time yield of 1 g/L/h without steroidal by-product, indicating the potential for site-specific and one-pot synthesis of steroid.
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Affiliation(s)
- Xinqi Xu
- Institute of Enzyme Catalysis and Synthetic Biotechnology, College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China
| | - Jinchang Zhong
- Institute of Enzyme Catalysis and Synthetic Biotechnology, College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China
| | - Bingmei Su
- Institute of Enzyme Catalysis and Synthetic Biotechnology, College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China
| | - Lian Xu
- Institute of Enzyme Catalysis and Synthetic Biotechnology, College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China
| | - Xiaokun Hong
- Institute of Enzyme Catalysis and Synthetic Biotechnology, College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China
| | - Juan Lin
- Institute of Enzyme Catalysis and Synthetic Biotechnology, College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China.
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Fathi Kisomi M, Yadegar A, Shekari T, Amin M, Llopis-Lorente A, Liu C, Haririan I, Aghdaei HA, Shokrgozar MA, Zali MR, Rad-Malekshahi M, Miri AH, Hamblin MR, Wacker MG. Unveiling the potential role of micro/nano biomaterials in the treatment of Helicobacter pylori infection. Expert Rev Anti Infect Ther 2024; 22:613-630. [PMID: 39210553 DOI: 10.1080/14787210.2024.2391910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/09/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Helicobacter pylori causes stubborn infections and leads to a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. Although antibiotic-based approaches have been widely used against H. pylori, some challenges such as antibiotic resistance are increasing in severity. Therefore, simpler but more effective strategies are needed. AREAS COVERED In this review, basic information on functionalized and non-functionalized micro/nano biomaterials and routes of administration for H. pylori inhibition are provided in an easy-to-understand format. Afterward, in vitro and in vivo studies of some promising bio-platforms including metal-based biomaterials, biopolymers, small-molecule saccharides, and vaccines for H. pylori inhibition are discussed in a holistic manner. EXPERT OPINION Functionalized or non-functionalized micro/nano biomaterials loaded with anti-H. pylori agents can show efficient bactericidal activity with no/slight negative influence on the host gastrointestinal microbiota. However, this claim needs to be substantiated with hard data such as assessment of the biopharmaceutical parameters of anti-H. pylori systems and the measurement of diversity/abundance of bacterial genera in the host gastric/gut microbiota before and after H. pylori eradication.
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Affiliation(s)
- Misagh Fathi Kisomi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tara Shekari
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Amin
- Department of Drug and Food Control, Faculty of Pharmacy, and the Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Antoni Llopis-Lorente
- Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Chenguang Liu
- College of Marine Life Science, Ocean University of China, Qingdao, P.R. China
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mazda Rad-Malekshahi
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Miri
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Matthias G Wacker
- Department of Pharmacy, Faculty of Science, National University of Singapore, 4 Science Drive 2, Singapore 117545, Singapore
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Gao P, Duan Z, Xu G, Gong Q, Wang J, Luo K, Chen J. Harnessing and Mimicking Bacterial Features to Combat Cancer: From Living Entities to Artificial Mimicking Systems. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2405075. [PMID: 39136067 DOI: 10.1002/adma.202405075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/23/2024] [Indexed: 08/29/2024]
Abstract
Bacterial-derived micro-/nanomedicine has garnered considerable attention in anticancer therapy, owing to the unique natural features of bacteria, including specific targeting ability, immunogenic benefits, physicochemical modifiability, and biotechnological editability. Besides, bacterial components have also been explored as promising drug delivery vehicles. Harnessing these bacterial features, cutting-edge physicochemical and biotechnologies have been applied to attenuated tumor-targeting bacteria with unique properties or functions for potent and effective cancer treatment, including strategies of gene-editing and genetic circuits. Further, the advent of bacteria-inspired micro-/nanorobots and mimicking artificial systems has furnished fresh perspectives for formulating strategies for developing highly efficient drug delivery systems. Focusing on the unique natural features and advantages of bacteria, this review delves into advances in bacteria-derived drug delivery systems for anticancer treatment in recent years, which has experienced a process from living entities to artificial mimicking systems. Meanwhile, a summary of relative clinical trials is provided and primary challenges impeding their clinical application are discussed. Furthermore, future directions are suggested for bacteria-derived systems to combat cancer.
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Affiliation(s)
- Peng Gao
- Department of General Surgery, Breast Disease Center, Department of Radiology, Huaxi MR Research Center (HMRRC), Liver Transplant Center, Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhenyu Duan
- Department of General Surgery, Breast Disease Center, Department of Radiology, Huaxi MR Research Center (HMRRC), Liver Transplant Center, Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China
| | - Gang Xu
- Department of General Surgery, Breast Disease Center, Department of Radiology, Huaxi MR Research Center (HMRRC), Liver Transplant Center, Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Qiyong Gong
- Department of General Surgery, Breast Disease Center, Department of Radiology, Huaxi MR Research Center (HMRRC), Liver Transplant Center, Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China
- Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, 361000, China
| | - Jing Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Kui Luo
- Department of General Surgery, Breast Disease Center, Department of Radiology, Huaxi MR Research Center (HMRRC), Liver Transplant Center, Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China
| | - Jie Chen
- Department of General Surgery, Breast Disease Center, Department of Radiology, Huaxi MR Research Center (HMRRC), Liver Transplant Center, Laboratory of Liver Transplantation, Key Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
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Tieu MV, Pham DT, Cho S. Bacteria-based cancer therapy: Looking forward. Biochim Biophys Acta Rev Cancer 2024; 1879:189112. [PMID: 38761983 DOI: 10.1016/j.bbcan.2024.189112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 03/25/2024] [Accepted: 05/10/2024] [Indexed: 05/20/2024]
Abstract
The field of bacteria-based cancer therapy, which focuses on the key role played by the prevalence of bacteria, specifically in tumors, in controlling potential targets for cancer therapy, has grown enormously over the past few decades. In this review, we discuss, for the first time, the global cancer situation and the timeline for using bacteria in cancer therapy. We also explore how interdisciplinary collaboration has contributed to the evolution of bacteria-based cancer therapies. Additionally, we address the challenges that need to be overcome for bacteria-based cancer therapy to be accepted in clinical trials and the latest advancements in the field. The groundbreaking technologies developed through bacteria-based cancer therapy have opened up new therapeutic strategies for a wide range of therapeutics in cancer.
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Affiliation(s)
- My-Van Tieu
- Department of Electronic Engineering, Gachon University, Seongnam-si 13120, Republic of Korea
| | - Duc-Trung Pham
- Department of Electronic Engineering, Gachon University, Seongnam-si 13120, Republic of Korea
| | - Sungbo Cho
- Department of Electronic Engineering, Gachon University, Seongnam-si 13120, Republic of Korea; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea.
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Chen A, Zhu J, Liu R, Mei Y, Li L, Fan Y, Ke Y, Liu B, Liu Q. Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells. Bioact Mater 2024; 37:331-347. [PMID: 38694762 PMCID: PMC11061616 DOI: 10.1016/j.bioactmat.2024.03.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 02/20/2024] [Accepted: 03/15/2024] [Indexed: 05/04/2024] Open
Abstract
Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells. In previous studies, FOLactis was designed, which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand, leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection. However, it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure. For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors, intratumoral injection is not feasible and peritumoral maybe a better choice. Herein, an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels. Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells (TEM), playing the role of artificial lymph island. Besides, administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors, resulting in an extended survival time. Therefore, these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.
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Affiliation(s)
- Aoxing Chen
- Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, The Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Junmeng Zhu
- The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Rui Liu
- The Comprehensive Cancer Centre, China Pharmaceutical University Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, 210008, China
| | - Yi Mei
- The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Lin Li
- The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Yue Fan
- The Comprehensive Cancer Centre, China Pharmaceutical University Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, 210008, China
| | - Yaohua Ke
- The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Baorui Liu
- Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, The Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
- The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Qin Liu
- Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, The Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
- The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
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Yang X, Nie W, Wang C, Fang Z, Shang L. Microfluidic-based multifunctional microspheres for enhanced oral co-delivery of probiotics and postbiotics. Biomaterials 2024; 308:122564. [PMID: 38581763 DOI: 10.1016/j.biomaterials.2024.122564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 03/16/2024] [Accepted: 04/01/2024] [Indexed: 04/08/2024]
Abstract
Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics (Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects. In vivo studies shown that the integrated multifunctional microspheres can significantly reduce intestinal inflammation, repair intestinal barrier function, enhance probiotic colonization in the intestine, and modulate disordered intestinal flora, demonstrating enhanced therapeutic effects in a mouse model of colitis. This work reveals that microfluidic-based smart droplet microspheres can provide a versatile platform for advanced microbial therapies.
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Affiliation(s)
- Xinyuan Yang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Weimin Nie
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Chong Wang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Zhonglin Fang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Luoran Shang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
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Xu KF, Wu SY, Wang Z, Guo Y, Zhu YX, Li C, Shan BH, Zhang X, Liu X, Wu FG. Hyperbaric oxygen enhances tumor penetration and accumulation of engineered bacteria for synergistic photothermal immunotherapy. Nat Commun 2024; 15:5147. [PMID: 38886343 PMCID: PMC11183253 DOI: 10.1038/s41467-024-49156-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 05/25/2024] [Indexed: 06/20/2024] Open
Abstract
Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.
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Affiliation(s)
- Ke-Fei Xu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Shun-Yu Wu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Zihao Wang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Yuxin Guo
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Ya-Xuan Zhu
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, P. R. China
| | - Chengcheng Li
- International Innovation Center for Forest Chemicals and Materials and Jiangsu Co-Innovation Center for Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, P. R. China
| | - Bai-Hui Shan
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Xinping Zhang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Xiaoyang Liu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China
| | - Fu-Gen Wu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing, 211189, P. R. China.
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Lu Q, Sun Y, Liang Z, Zhang Y, Wang Z, Mei Q. Nano-optogenetics for Disease Therapies. ACS NANO 2024; 18:14123-14144. [PMID: 38768091 DOI: 10.1021/acsnano.4c00698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Optogenetic, known as the method of 21 centuries, combines optic and genetic engineering to precisely control photosensitive proteins for manipulation of a broad range of cellular functions, such as flux of ions, protein oligomerization and dissociation, cellular intercommunication, and so on. In this technique, light is conventionally delivered to targeted cells through optical fibers or micro light-emitting diodes, always suffering from high invasiveness, wide-field illumination facula, strong absorption, and scattering by nontargeted endogenous substance. Light-transducing nanomaterials with advantages of high spatiotemporal resolution, abundant wireless-excitation manners, and easy functionalization for recognition of specific cells, recently have been widely explored in the field of optogenetics; however, there remain a few challenges to restrain its clinical applications. This review summarized recent progress on light-responsive genetically encoded proteins and the myriad of activation strategies by use of light-transducing nanomaterials and their disease-treatment applications, which is expected for sparking helpful thought to push forward its preclinical and translational uses.
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Affiliation(s)
- Qi Lu
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China
| | - Yaru Sun
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China
| | - Zhengbing Liang
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China
| | - Yi Zhang
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China
| | - Zhigang Wang
- Department of Critical Care Medicine, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, China
| | - Qingsong Mei
- Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China
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Xia X, Zhang JW, Zhao B, Zhang M, Chen ZR, Zhang BF, Ji YL, Wang X, Xiong WM, Li JW, Lv QL. Progress of engineered bacteria for tumour therapy. Int Immunopharmacol 2024; 132:111935. [PMID: 38599096 DOI: 10.1016/j.intimp.2024.111935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 03/14/2024] [Accepted: 03/24/2024] [Indexed: 04/12/2024]
Abstract
Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.
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Affiliation(s)
- Xue Xia
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China; College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China
| | - Jing-Wen Zhang
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China; College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China
| | - Bing Zhao
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China; College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China
| | - Min Zhang
- Nanchang Inspection and Testing Center, Nanchang Key Laboratory for Quality and Safety Risk Assessment of Health Food and its Contact Materials, Nanchang 330012, PR China
| | - Zhang-Ren Chen
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang 330000, PR China
| | - Bing-Feng Zhang
- College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China
| | - Yu-Long Ji
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China
| | - Xia Wang
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China
| | - Wen-Min Xiong
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China
| | - Jia-Wei Li
- Department of Cardiovascular, The First Affiliated Hospital of Nanchang University, Jiangxi, PR China.
| | - Qiao-Li Lv
- Jiangxi Key Laboratory of Translational Cancer Research, NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi 330029, PR China; College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China.
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Zhou Y, Li Q, Wu Y, Zhang W, Ding L, Ji C, Li P, Chen T, Feng L, Tang BZ, Huang X. Synergistic Brilliance: Engineered Bacteria and Nanomedicine Unite in Cancer Therapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2313953. [PMID: 38400833 DOI: 10.1002/adma.202313953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/21/2024] [Indexed: 02/26/2024]
Abstract
Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, and producing anticancer microbial agents in situ to suppress tumor growth. Despite the unique advantages of bacteria-based cancer biotherapy, the insufficient treatment efficiency limits its application in the complete ablation of malignant tumors. The combination of nanomedicine and engineered bacteria has attracted increasing attention owing to their striking synergistic effects in cancer treatment. Engineered bacteria that function as natural vehicles can effectively deliver nanomedicines to tumor sites. Moreover, bacteria provide an opportunity to enhance nanomedicines by modulating the TME and producing substrates to support nanomedicine-mediated anticancer reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, and catalytic properties, and plays an important role in promoting bacteria-mediated biotherapies. The synergistic anticancer effects of engineered bacteria and nanomedicines in cancer therapy are comprehensively summarized in this review. Attention is paid not only to the fabrication of nanobiohybrid composites, but also to the interpromotion mechanism between engineered bacteria and nanomedicine in cancer therapy. Additionally, recent advances in engineered bacteria-synergized multimodal cancer therapies are highlighted.
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Affiliation(s)
- Yaofeng Zhou
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Nanchang University, Nanchang, 330047, P. R. China
| | - Qianying Li
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Nanchang University, Nanchang, 330047, P. R. China
| | - Yuhao Wu
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Nanchang University, Nanchang, 330047, P. R. China
| | - Wan Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, P. R. China
| | - Lu Ding
- Department of Cardiology, Jiangxi Hypertension Research Institute, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, P. R. China
| | - Chenlin Ji
- School of Engineering, Westlake University, Hangzhou, 310030, P. R. China
| | - Ping Li
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Nanchang University, Nanchang, 330047, P. R. China
| | - Tingtao Chen
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, 330036, P. R. China
| | - Lili Feng
- Key Laboratory of Superlight Materials and Surface Technology Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China
| | - Ben Zhong Tang
- School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong, 518172, P. R. China
| | - Xiaolin Huang
- State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Nanchang University, Nanchang, 330047, P. R. China
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Zhu L, Yu T, Wang W, Xu T, Geng W, Li N, Zan X. Responsively Degradable Nanoarmor-Assisted Super Resistance and Stable Colonization of Probiotics for Enhanced Inflammation-Targeted Delivery. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2308728. [PMID: 38241751 DOI: 10.1002/adma.202308728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 12/09/2023] [Indexed: 01/21/2024]
Abstract
Manipulation of the gut microbiota using oral microecological preparations has shown great promise in treating various inflammatory disorders. However, delivering these preparations while maintaining their disease-site specificity, stability, and therapeutic efficacy is highly challenging due to the dynamic changes associated with pathological microenvironments in the gastrointestinal tract. Herein, a superior armored probiotic with an inflammation-targeting capacity is developed to enhance the efficacy and timely action of bacterial therapy against inflammatory bowel disease (IBD). The coating strategy exhibits suitability for diverse probiotic strains and has negligible influence on bacterial viability. This study demonstrates that these armored probiotics have ultraresistance to extreme intraluminal conditions and stable mucoadhesive capacity. Notably, the HA-functionalized nanoarmor equips the probiotics with inflamed-site targetability through multiple interactions, thus enhancing their efficacy in IBD therapy. Moreover, timely "awakening" of ingested probiotics through the responsive transferrin-directed degradation of the nanoarmor at the site of inflammation is highly beneficial for bacterial therapy, which requires the bacterial cells to be fully functional. Given its easy preparation and favorable biocompatibility, the developed single-cell coating approach provides an effective strategy for the advanced delivery of probiotics for biomedical applications at the cellular level.
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Affiliation(s)
- Limeng Zhu
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325000, China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China
- College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Tiantian Yu
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China
| | - Wenchao Wang
- Department of Pain, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Tong Xu
- College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China
- State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China
| | - Wujun Geng
- Department of Pain, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Na Li
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China
| | - Xingjie Zan
- School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325000, China
- Wenzhou Key Laboratory of Perioperative Medicine, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China
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Han J, McClements DJ, Liu X, Liu F. Oral delivery of probiotics using single-cell encapsulation. Compr Rev Food Sci Food Saf 2024; 23:e13322. [PMID: 38597567 DOI: 10.1111/1541-4337.13322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 02/01/2024] [Accepted: 02/28/2024] [Indexed: 04/11/2024]
Abstract
Adequate intake of live probiotics is beneficial to human health and wellbeing because they can help treat or prevent a variety of health conditions. However, the viability of probiotics is reduced by the harsh environments they experience during passage through the human gastrointestinal tract (GIT). Consequently, the oral delivery of viable probiotics is a significant challenge. Probiotic encapsulation provides a potential solution to this problem. However, the production methods used to create conventional encapsulation technologies often damage probiotics. Moreover, the delivery systems produced often do not have the required physicochemical attributes or robustness for food applications. Single-cell encapsulation is based on forming a protective coating around a single probiotic cell. These coatings may be biofilms or biopolymer layers designed to protect the probiotic from the harsh gastrointestinal environment, enhance their colonization, and introduce additional beneficial functions. This article reviews the factors affecting the oral delivery of probiotics, analyses the shortcomings of existing encapsulation technologies, and highlights the potential advantages of single-cell encapsulation. It also reviews the various approaches available for single-cell encapsulation of probiotics, including their implementation and the characteristics of the delivery systems they produce. In addition, the mechanisms by which single-cell encapsulation can improve the oral bioavailability and health benefits of probiotics are described. Moreover, the benefits, limitations, and safety issues of probiotic single-cell encapsulation technology for applications in food and beverages are analyzed. Finally, future directions and potential challenges to the widespread adoption of single-cell encapsulation of probiotics are highlighted.
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Affiliation(s)
- Jiaqi Han
- College of Food Science and Engineering, Northwest A&F University, Xianyang, Shaanxi, China
| | - David Julian McClements
- Department of Food Science, University of Massachusetts Amherst, Amherst, Massachusetts, USA
| | - Xuebo Liu
- College of Food Science and Engineering, Northwest A&F University, Xianyang, Shaanxi, China
| | - Fuguo Liu
- College of Food Science and Engineering, Northwest A&F University, Xianyang, Shaanxi, China
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41
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Fu Y, Li J, Cai W, Huang Y, Liu X, Ma Z, Tang Z, Bian X, Zheng J, Jiang J, Li C. The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions. Acta Pharm Sin B 2024; 14:1560-1591. [PMID: 38572104 PMCID: PMC10985043 DOI: 10.1016/j.apsb.2023.11.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 10/20/2023] [Accepted: 11/03/2023] [Indexed: 04/05/2024] Open
Abstract
Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i.e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments.
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Affiliation(s)
- Yu Fu
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Jia Li
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Wenyun Cai
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Yulan Huang
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Xinlong Liu
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Zhongyi Ma
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Zhongjie Tang
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Xufei Bian
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Ji Zheng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Jiayun Jiang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Chong Li
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
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Yang EL, Sun ZJ. Nanomedicine Targeting Myeloid-Derived Suppressor Cells Enhances Anti-Tumor Immunity. Adv Healthc Mater 2024; 13:e2303294. [PMID: 38288864 DOI: 10.1002/adhm.202303294] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/27/2023] [Indexed: 02/13/2024]
Abstract
Cancer immunotherapy, a field within immunology that aims to enhance the host's anti-cancer immune response, frequently encounters challenges associated with suboptimal response rates. The presence of myeloid-derived suppressor cells (MDSCs), crucial constituents of the tumor microenvironment (TME), exacerbates this issue by fostering immunosuppression and impeding T cell differentiation and maturation. Consequently, targeting MDSCs has emerged as crucial for immunotherapy aimed at enhancing anti-tumor responses. The development of nanomedicines specifically designed to target MDSCs aims to improve the effectiveness of immunotherapy by transforming immunosuppressive tumors into ones more responsive to immune intervention. This review provides a detailed overview of MDSCs in the TME and current strategies targeting these cells. Also the benefits of nanoparticle-assisted drug delivery systems, including design flexibility, efficient drug loading, and protection against enzymatic degradation, are highlighted. It summarizes advances in nanomedicine targeting MDSCs, covering enhanced treatment efficacy, safety, and modulation of the TME, laying the groundwork for more potent cancer immunotherapy.
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Affiliation(s)
- En-Li Yang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei, 430079, China
| | - Zhi-Jun Sun
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei, 430079, China
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Wang L, Liu J. Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics. Acc Chem Res 2024; 57:945-956. [PMID: 38422996 DOI: 10.1021/acs.accounts.3c00798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
Bacteria-based therapy has spotlighted an unprecedented potential in treating a range of diseases, given that bacteria can be used as both drug vehicles and therapeutic agents. However, the use of bacteria for disease treatment often suffers from unsatisfactory outcomes, due largely to their suboptimal bioavailability, dose-dependent toxicity, and low targeting colonization. In the past few years, substantial efforts have been devoted to tackling these difficulties, among which methods capable of integrating bacteria with multiple functions have been extensively pursued. Different from conventional genetic engineering and modern synthetic bioengineering, surface modification of bacteria has emerged as a simple yet flexible strategy to introduce different functional motifs. Polydopamine, which can be easily formed via in situ dopamine oxidation and self-polymerization, is an appealing biomimetic polymer that has been widely applied for interfacial modification and functionalization. By virtue of its catechol groups, polydopamine can be efficiently codeposited with a multitude of functional elements on diverse surfaces.In this Account, we summarize the recent advances from our group with a focus on the interfacial polymerization-mediated functionalization of bacteria for advanced microbial therapy. First, we present the optimized strategy for bacterial surface modification under cytocompatible conditions by in situ dopamine polymerization. Taking advantage of the hydrogen bonding, π-π stacking, Michael addition, and Schiff base reaction with polydopamine, diverse functional small molecules and macromolecules are facilely codeposited onto the bacterial surface. Namely, monomodal, dual-modal, and multimodal surface modification of bacteria can be achieved by dopamine self-deposition, codeposition with a unitary composition, and codeposition with a set of multiple components, respectively. Second, we outline the regulation of bacterial functions by surface modification. The formed polydopamine surface endows bacteria with the ability to resist in vivo insults, such as gastrointestinal tract stressors and immune clearance, resulting in greatly improved bioavailability. Integration with specific ligands or therapeutic components enables the modified bacteria to increase targeting accumulation and colonization at lesion sites or play synergistic effects in disease treatment. Bacteria codeposited with different bioactive moieties, such as protein antigens, antibodies, and immunoadjuvants, are even able to actively interact with the host, particularly to elicit immune responses by either suppressing immune overactivation to promote the reversion of pathological inflammations or provoking protective innate and/or adaptive immunity to inhibit pathogenic invaders. Third, we highlight the applications of surface-modified bacteria as multifunctional living therapeutics in disease treatment, especially alleviating inflammatory bowel diseases via oral delivery and intervening in different types of cancer through systemic or intratumoral injection. Finally, we discuss the challenges and prospects of dopamine polymerization-mediated multifunctionalization for preparing advanced bacterial therapeutics as well as their bench to bedside translation. We anticipate that this Account can provide an insightful overview of bacterial therapy and inspire innovative thinking and new efforts to develop next-generation living therapeutics for treating various diseases.
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Affiliation(s)
- Lu Wang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jinyao Liu
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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Wang Z, Sun W, Hua R, Wang Y, Li Y, Zhang H. Promising dawn in tumor microenvironment therapy: engineering oral bacteria. Int J Oral Sci 2024; 16:24. [PMID: 38472176 PMCID: PMC10933493 DOI: 10.1038/s41368-024-00282-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 01/06/2024] [Accepted: 01/07/2024] [Indexed: 03/14/2024] Open
Abstract
Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.
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Affiliation(s)
- Zifei Wang
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, China
| | - Wansu Sun
- Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ruixue Hua
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, China
| | - Yuanyin Wang
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, China
| | - Yang Li
- Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
| | - Hengguo Zhang
- Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, China.
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Chen M, Han Q, Zhang M, Liu Y, Wang L, Yang F, Li Q, Cao Z, Fan C, Liu J. Upconversion dual-photosensitizer-expressing bacteria for near-infrared monochromatically excitable synergistic phototherapy. SCIENCE ADVANCES 2024; 10:eadk9485. [PMID: 38446879 PMCID: PMC11326044 DOI: 10.1126/sciadv.adk9485] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 01/29/2024] [Indexed: 03/08/2024]
Abstract
Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer-expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.
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Affiliation(s)
- Mian Chen
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qiuju Han
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Mengmeng Zhang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Ying Liu
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Lu Wang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Fengmin Yang
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Qian Li
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Zhenping Cao
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Chunhai Fan
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jinyao Liu
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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Chen Z, Liu Y, Yu Y, Yang S, Feng J, Zhu Y, Huang W, Qin B, Guan X, He Z, Sun M, Sun J. Micro-to-Nano Oncolytic Microbial System Shifts from Tumor Killing to Tumor Draining Lymph Nodes Remolding for Enhanced Immunotherapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2306488. [PMID: 37844257 DOI: 10.1002/adma.202306488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 09/08/2023] [Indexed: 10/18/2023]
Abstract
Because the tumor-draining lymph nodes (TDLNs) microenvironment is commonly immunosuppressive, oncolytic microbe-induced tumor antigens aren't sufficiently cross-primed tumor specific T cells through antigen-presenting cells (e.g., dendritic cells (DCs)) in TDLNs. Herein, this work develops the micro-to-nano oncolytic microbial therapeutics based on pyranose oxidase (P2 O) overexpressed Escherichia coli (EcP) which are simultaneously encapsulated by PEGylated mannose and low-concentrated photosensitizer nanoparticles (NPs). Following administration, P2 O from this system generates toxic hydrogen peroxide for tumor regression and leads to the release of tumor antigens. The "microscale" EcP is triggered, following exposure to the laser irradiation, to secrete the "nanoscale" bacterial outer membrane vesicles (OMVs). The enhanced TDLNs delivery via OMVs significantly regulates the TDLNs immunomicroenvironment, promoting the maturation of DCs to potentiate tumor antigen-specific T cells immune response. The micro-to-nano oncolytic microbe is leveraged to exert tumor killing and remold TDLNs for initiating potent activation of DCs, providing promising strategies to facilitate microbial cancer vaccination.
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Affiliation(s)
- Zhichao Chen
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Yuhan Liu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Yuxuan Yu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Shihua Yang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang, Liaoning, 110001, China
| | - Jing Feng
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Yinmei Zhu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Wanxu Huang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Bin Qin
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Xinyao Guan
- Experimental Teaching Center, Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Zhonggui He
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Mengchi Sun
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
| | - Jin Sun
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
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Han M, Lei W, Liang J, Li H, Hou M, Gao Z. The single-cell modification strategies for probiotics delivery in inflammatory bowel disease: A review. Carbohydr Polym 2024; 324:121472. [PMID: 37985038 DOI: 10.1016/j.carbpol.2023.121472] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/06/2023] [Accepted: 10/07/2023] [Indexed: 11/22/2023]
Abstract
Oral probiotic therapy has become an increasingly attractive method for treating various diseases, including intestinal barrier dysfunction, inflammatory bowel disease (IBD), and colorectal cancer due to its safety and convenience. However, only a few probiotics after oral gavage can survive the acidic and bile salt conditions of the gastrointestinal tract and colonize the colon to have a nutritional effect on the host. To address these challenges, encapsulation technology has been applied to protect probiotics from harsh gastrointestinal conditions, improve gut adhesion, and reduce immunogenicity. In addition, some of the functional polysaccharides are used to endow probiotics with exogenous functions as prebiotics. In this review, we systematically introduced the advancements of emerging single-cell modification strategies for probiotics in IBD applications. Additionally, we discussed the limitations and perspectives of single-cell modification strategies for probiotics. This review contributed to the development of probiotic delivery systems with higher therapeutic efficacy against colitis.
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Affiliation(s)
- Mengzhen Han
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Wenzhi Lei
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Jingjing Liang
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Hongcai Li
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Mengxin Hou
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China.
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48
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Wu L, Du Z, Li L, Qiao L, Zhang S, Yin X, Chang X, Li C, Hua Z. Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy. Signal Transduct Target Ther 2024; 9:14. [PMID: 38195682 PMCID: PMC10776584 DOI: 10.1038/s41392-023-01703-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/17/2023] [Accepted: 11/08/2023] [Indexed: 01/11/2024] Open
Abstract
Live bacteria-mediated antitumor therapies mark a pivotal point in cancer immunotherapy. However, the difficulty in reconciling the safety and efficacy of bacterial therapies has limited their application. Improving bacterial tumor-targeted delivery while maintaining biosafety is a critical hurdle for the clinical translation of live microbial therapy for cancer. Here, we developed "dead" yet "functional" Salmonella-loaded macrophages using liquid nitrogen cold shock of an attenuated Salmonella typhimurium VNP20009-contained macrophage cell line. The obtained "dead" macrophages achieve an average loading of approximately 257 live bacteria per 100 cells. The engineered cells maintain an intact cellular structure but lose their original pathogenicity, while intracellular bacteria retain their original biological activity and are delay freed, followed by proliferation. This "Trojan horse"-like bacterial camouflage strategy avoids bacterial immunogenicity-induced neutrophil recruitment and activation in peripheral blood, reduces the clearance of bacteria by neutrophils and enhances bacterial tumor enrichment efficiently after systemic administration. Furthermore, this strategy also strongly activated the tumor microenvironment, including increasing antitumor effector cells (including M1-like macrophages and CD8+ Teffs) and decreasing protumor effector cells (including M2-like macrophages and CD4+ Tregs), and ultimately improved antitumor efficacy in a subcutaneous H22 tumor-bearing mouse model. The cryo-shocked macrophage-mediated bacterial delivery strategy holds promise for expanding the therapeutic applications of living bacteria for cancer.
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Affiliation(s)
- Leyang Wu
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
- Nanjing Generecom Biotechnology Co., Ltd, Nanjing, 210023, China
- Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc, Changzhou, 213164, Jiangsu, China
| | - Zengzheng Du
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Lin Li
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Liyuan Qiao
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Shuhui Zhang
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Xingpeng Yin
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Xiaoyao Chang
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Chenyang Li
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China
| | - Zichun Hua
- The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital, School of Life Sciences and The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, 21008, Jiangsu, China.
- Nanjing Generecom Biotechnology Co., Ltd, Nanjing, 210023, China.
- Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc, Changzhou, 213164, Jiangsu, China.
- School of Biopharmacy, China Pharmaceutical University, Nanjing, 210023, Jiangsu, China.
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Alsharedeh R, Alshraiedeh N, Aljabali AA, Tambuwala MM. Magnetosomes as Potential Nanocarriers for Cancer Treatment. Curr Drug Deliv 2024; 21:1073-1081. [PMID: 37340750 DOI: 10.2174/1567201820666230619155528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/13/2023] [Accepted: 05/19/2023] [Indexed: 06/22/2023]
Abstract
Magnetotactic bacteria (MTBs) and their organelles, magnetosomes, are intriguing options that might fulfill the criteria of using bacterial magnetosomes (BMs). The ferromagnetic crystals contained in BMs can condition the magnetotaxis of MTBs, which is common in water storage facilities. This review provides an overview of the feasibility of using MTBs and BMs as nanocarriers in cancer treatment. More evidence suggests that MTBs and BMs can be used as natural nanocarriers for conventional anticancer medicines, antibodies, vaccine DNA, and siRNA. In addition to improving the stability of chemotherapeutics, their usage as transporters opens the possibilities for the targeted delivery of single ligands or combinations of ligands to malignant tumors. Magnetosome magnetite crystals are different from chemically made magnetite nanoparticles (NPs) because they are strong single-magnetic domains that stay magnetized even at room temperature. They also have a narrow size range and a uniform crystal morphology. These chemical and physical properties are essential for their usage in biotechnology and nanomedicine. Bioremediation, cell separation, DNA or antigen regeneration, therapeutic agents, enzyme immobilization, magnetic hyperthermia, and contrast enhancement of magnetic resonance are just a few examples of the many uses for magnetite-producing MTB, magnetite magnetosomes, and magnetosome magnetite crystals. From 2004 to 2022, data mining of the Scopus and Web of Science databases showed that most research using magnetite from MTB was carried out for biological reasons, such as in magnetic hyperthermia and drug delivery.
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Affiliation(s)
- Rawan Alsharedeh
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid 21163 - P. O. BOX 566, Jordan
| | - Nid'a Alshraiedeh
- Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid, Jordan
| | - Alaa A Aljabali
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid 21163 - P. O. BOX 566, Jordan
| | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, UK
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50
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Zhou M, Yin Y, Zhao J, Zhou M, Bai Y, Zhang P. Applications of microalga-powered microrobots in targeted drug delivery. Biomater Sci 2023; 11:7512-7530. [PMID: 37877241 DOI: 10.1039/d3bm01095c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2023]
Abstract
Over the past decade, researchers have proposed a new class of drug delivery systems, bio-hybrid micro-robots, designed with a variety of living cell-driven micro-robots that utilize the unique mobility of natural organisms (bacteria, cells, exosomes, etc.) to transport effective drugs. Microalgae are considered potential drug delivery carriers. Recent studies have shown that microalga-based drug delivery systems exhibit excellent biocompatibility. In addition, microalgae have a large surfactant area, phototaxis, oxygen production, and other characteristics, so they are used as a carrier for the treatment of bacterial infections, cancer, etc. This review summarizes the modification of microalgae including click chemistry and electrostatic adsorption, and can improve the drug loading efficiency through dehydration and hydration strategies. The prepared microalgal drug delivery system can be targeted to different organs by different dosing methods or using external forces. Finally, it summarizes its antibacterial (gastritis, periodontitis, skin wound inflammation, etc.) and antitumor applications.
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Affiliation(s)
- Min Zhou
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Yannan Yin
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Jiuhong Zhao
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
| | - Mingyang Zhou
- Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA
| | - Yanjie Bai
- Department of Stomatology, People's Hospital of Liaoning Province, Shenyang 110016, China.
| | - Peng Zhang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
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