1
|
Wang A, Wang X, Li D, Li A, He M, Yuan Y, Ye L, Liu J. A superior method for antitumor therapy and application: dual-ligand nanomedicines. J Mater Chem B 2025. [PMID: 40396464 DOI: 10.1039/d5tb00044k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
Currently, nanomedicines have been widely applied in the treatment of various types of tumors. However, due to the complexity of the tumor microenvironment, conventional nanomedicines often exhibit poor efficacy, insufficient site specificity, and susceptibility to off-target effects. In contrast, dual-ligand nanomedicines demonstrate superior targeting ability and drug penetration in tumor therapy. These nanomedicines are equipped with two ligands on their surface, enabling targeting of specific receptors on the same or different cells. The specific binding between ligands and receptors significantly enhances the selectivity and targeting of dual-ligand nanomedicines towards tumors. This review systematically describes the preparation of dual-ligand nanomedicines, the influencing factors, and the types of delivered drugs, focusing on the application of dual-ligand nanomedicines in targeting the treatment of various tumors. We highlight the comprehensiveness of dual-ligand nanomedicines for the treatment of tumors, including glioblastoma, lung cancer, breast cancer, gastric cancer, and many other types of tumors. Finally, the possible challenges for the future development of dual-ligand nanomedicines in terms of preparation, clinic, and safety are further analyzed. We look forward to exploring dual-ligand nanomedicines in greater depth to provide references for their future development and clinical applications.
Collapse
Affiliation(s)
- Ailing Wang
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
| | - Xuejun Wang
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
| | - Dan Li
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
| | - Aixue Li
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
| | - Mengyuan He
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
| | - Yingying Yuan
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
- College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Li Ye
- School of Pharmacy and (R & D Center) Lab. for Drug Discovery from Natural Resource, Macau University of Science and Technology, Macau SAR, 999078, China.
| | - Jiyong Liu
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Department of Pharmacy, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China
| |
Collapse
|
2
|
Wang S, Li J, Zhang Z, Cao S, Zhang Z, Bian Y, Xu Y, Ma C. Advances in nanomedicine and delivery systems for gastric cancer research. Front Bioeng Biotechnol 2025; 13:1565999. [PMID: 40190709 PMCID: PMC11968739 DOI: 10.3389/fbioe.2025.1565999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open
Abstract
The early diagnosis rate of gastric cancer is low, and most patients are already at an advanced stage by the time they are diagnosed, posing significant challenges for treatment and exhibiting high recurrence rates, which notably diminish patients' survival time and quality of life. Therefore, there is an urgent need to identify methods that can enhance treatment efficacy. Nanomedicine, distinguished by its small size, high targeting specificity, and strong biological compatibility, is particularly well-suited to address the toxic side effects associated with current diagnostic and therapeutic approaches for gastric cancer. Consequently, the application of nanomedicine and delivery systems in the diagnosis and treatment of gastric cancer has garnered increasing interest from researchers. This review provides an overview of recent advancements in the use of nanomaterials as drugs or drug delivery systems in gastric cancer research, encompassing their applications in diagnosis, chemotherapy, radiotherapy, surgery, and phototherapy, and explores the promising prospects of nanomedicine in the treatment of gastric cancer.
Collapse
Affiliation(s)
- Sizhe Wang
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Jilei Li
- Henan Province Hospital of TCM, Zhengzhou(The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Zhenyu Zhang
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Shasha Cao
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Zihan Zhang
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Yifan Bian
- Henan University of Chinese Medicine(The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Yanchao Xu
- Henan Province Hospital of TCM, Zhengzhou(The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| | - Chunzheng Ma
- Henan Province Hospital of TCM, Zhengzhou(The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, China
| |
Collapse
|
3
|
Shah SAR, Mumtaz M, Sharif S, Mustafa I, Nayila I. Helicobacter pylori and gastric cancer: current insights and nanoparticle-based interventions. RSC Adv 2025; 15:5558-5570. [PMID: 39967885 PMCID: PMC11834156 DOI: 10.1039/d4ra07886a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 02/07/2025] [Indexed: 02/20/2025] Open
Abstract
Background: H. pylori is recognized as one of the main causes of gastric cancer, and this type of cancer is considered as one of the leading diseases causing cancer deaths all over the world. Knowledge on the interactions between H. pylori and gastric carcinogenesis is important for designing preventive measures. Objective: the objective of this review is to summarize the available literature on H. pylori and gastric cancer, specifically regarding the molecular mechanisms, nanoparticle-based therapy and clinical developments. Methods: the databases including PubMed, Google Scholar and web of science were searched as well as papers from 2010 to 2024 were considered for review. Research literature on H. pylori, gastric cancer, nanoparticles, nanomedicine, and therapeutic interventions was summarized for current findings and possible treatments. Results: the presence of H. pylori in gastric mucosa causes chronic inflammation and several molecular alterations such as DNA alteration, epigenetic changes and activation of oncogenic signaling pathways which causes gastric carcinogenesis. Conventional antibiotic treatments have some issues because of the constantly rising levels of antibiotic resistance. Lipid based nanoformulations, polymeric and metallic nanoparticles have been delivered in treatment of H. pylori to improve drug delivery and alter immunological responses. Conclusion: nanoparticle based interventions have been widely explored as drug delivery systems by improving the treatment strategies against H. pylori induced gastric cancer. Further studies and clinical trials are required to bring these findings into a clinical setting in order to possibly alter the management of H. pylori related gastric malignancies.
Collapse
Affiliation(s)
- Syed Ali Raza Shah
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore Lahore Pakistan
| | - Maria Mumtaz
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore Lahore Pakistan
| | - Sumaira Sharif
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore Lahore Pakistan
| | - Imtiaz Mustafa
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore Lahore Pakistan
| | - Iffat Nayila
- Department of Pharmacy, The University of Lahore Sargodha Campus Sargodha Pakistan
| |
Collapse
|
4
|
Teimouri M, Homayouni Tabrizi M, Karimi E. The selective proapoptotic impact of the myricetin-loaded alginate-cellulose hybrid nanocrystals (MAC-NCs) on the human AGS gastric cancer cells. Mol Biol Rep 2024; 51:998. [PMID: 39299971 DOI: 10.1007/s11033-024-09864-0] [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: 05/13/2024] [Accepted: 08/14/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Myricetin, a flavanol present in fruits, tea, and vegetables, has the potential to reduce chronic diseases like gastric cancer by promoting cell death and stopping cell growth. However, its limited bioactivity due to its short lifespan and poor solubility in water has been a challenge. The current research focuses on incorporating myricetin into alginate-cellulose hybrid nanocrystals to enhance its selective proapoptotic effects on human AGS gastric cancer cells. METHODS MAC-NCs, myricetin-loaded alginate-cellulose hybrid nanocrystals, were synthesized using a combined co-precipitation/ultrasonic homogenization method and characterized through Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscope (FESEM), and Zeta-potential analyses. Their cytotoxic activity was tested on cancerous (AGS) and normal (Huvec) cells, revealing selective toxicity. Apoptotic markers, Caspase 8 and Caspase 9, gene expression was measured, and cell death type was confirmed using DAPI staining and flow cytometry on AGS cells. RESULTS Synthesized MAC-NCs, measuring 40 nm, showed significant selective toxicity on human gastric cells (IC50 of 31.05 µg/mL) compared to normal endothelial cells (IC50 of 214.26 µg/mL). DAPI and annexin flow cytometry revealed increased apoptotic bodies in gastric cells, indicating apoptosis. However, the apoptosis was found to be independent of Caspase-8 and Caspase-9. CONCLUSION The current study provides critical insights into the therapeutic potential of MAC-NCs for gastric cancer treatment. Based on the notable induction of apoptosis in the AGS cancer cell line, the synthesized MAC-NCs exhibit promising potential as a selective anti-gastric cancer agent. However, further in-vivo studies are necessary to confirm and quantify the nanoparticle's selective toxicity and pharmaceutical properties in future investigations.
Collapse
Affiliation(s)
- Mahdieh Teimouri
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | | | - Ehsan Karimi
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| |
Collapse
|
5
|
Liu BN, Gao XL, Piao Y. Mapping the intellectual structure and emerging trends for the application of nanomaterials in gastric cancer: A bibliometric study. World J Gastrointest Oncol 2024; 16:2181-2199. [PMID: 38764848 PMCID: PMC11099444 DOI: 10.4251/wjgo.v16.i5.2181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 02/11/2024] [Accepted: 03/21/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials. However, the research hotspots and trends in the application of nanomaterials in gastric cancer (GC) remain obscure. AIM To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC. METHODS Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study. VOSviewer and CiteSpace were used for bibliometric and visualization analyses. RESULTS From 2000 to 2022, the application of nanomaterials in GC developed rapidly. The keyword co-occurrence analysis showed that the related research topics were divided into three clusters: (1) The application of nanomaterials in GC treatment; (2) The application and toxicity of nanomaterials in GC diagnosis; and (3) The effects of nanomaterials on the biological behavior of GC cells. Complexes, silver nanoparticles, and green synthesis are the latest high-frequency keywords that represent promising future research directions. CONCLUSION The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.
Collapse
Affiliation(s)
- Bo-Na Liu
- Department of Oncology, General Hospital of Northern Theater Command, Shenyang 110015, Liaoning Province, China
| | - Xiao-Li Gao
- Department of Oncology, General Hospital of Northern Theater Command, Shenyang 110015, Liaoning Province, China
| | - Ying Piao
- Department of Oncology, General Hospital of Northern Theater Command, Shenyang 110015, Liaoning Province, China
| |
Collapse
|
6
|
Garg A, Karhana S, Khan MA. Nanomedicine for the eradication of Helicobacter pylori: recent advances, challenges and future perspective. Future Microbiol 2024; 19:431-447. [PMID: 38381027 DOI: 10.2217/fmb-2023-0189] [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: 08/23/2023] [Accepted: 10/31/2023] [Indexed: 02/22/2024] Open
Abstract
Helicobacter pylori infection is linked to gastritis, ulcers and gastric cancer. Nanomedicine offers a promising solution by utilizing nanoparticles for precise drug delivery, countering antibiotic resistance and delivery issues. Nanocarriers such as liposomes and nanoparticles enhance drug stability and circulation, targeting infection sites through gastric mucosa characteristics. Challenges include biocompatibility, stability, scalability and personalized therapies. Despite obstacles, nanomedicine's potential for reshaping H. pylori eradication is significant and showcased in this review focusing on benefits, limitations and future prospects of nanomedicine-based strategies.
Collapse
Affiliation(s)
- Aakriti Garg
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Sonali Karhana
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| | - Mohd A Khan
- Centre for Translational & Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India
| |
Collapse
|
7
|
Gupta A, Shetty S, Mutalik S, Chandrashekar H R, K N, Mathew EM, Jha A, Mishra B, Rajpurohit S, Ravi G, Saha M, Moorkoth S. Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation. Heliyon 2023; 9:e20406. [PMID: 37810864 PMCID: PMC10550623 DOI: 10.1016/j.heliyon.2023.e20406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/10/2023] Open
Abstract
Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.
Collapse
Affiliation(s)
- Ashutosh Gupta
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Srinivas Mutalik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Raghu Chandrashekar H
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Nandakumar K
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Elizabeth Mary Mathew
- School of Pharmacy, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Abhishek Jha
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Brahmeshwar Mishra
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Siddheesh Rajpurohit
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Gundawar Ravi
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Moumita Saha
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Sudheer Moorkoth
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| |
Collapse
|
8
|
Mosallam FM, Bendary MM, Elshimy R, El-Batal AI. Curcumin clarithromycin nano-form a promising agent to fight Helicobacter pylori infections. World J Microbiol Biotechnol 2023; 39:324. [PMID: 37773301 PMCID: PMC10541836 DOI: 10.1007/s11274-023-03745-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 08/28/2023] [Indexed: 10/01/2023]
Abstract
Helicobacter pylori (H. pylori) is the main cause of gastric diseases. However, the traditional antibiotic treatment of H. pylori is limited due to increased antibiotic resistance, low efficacy, and low drug concentration in the stomach. This study developed a Nano-emulsion system with ability to carry Curcumin and Clarithromycin to protect them against stomach acidity and increase their efficacy against H. pylori. We used oil in water emulsion system to prepare a novel Curcumin Clarithromycin Nano-Emulsion (Cur-CLR-NE). The nano-emulsion was validated by dynamic light scattering (DLS) technique, zeta potential; transmission electron microscopy (mean particle size 48 nm), UV-visible scanning and Fourier transform infrared spectroscopy (FT-IR). The in vitro assay of Cur-CLR-NE against H. pylori was evaluated by minimum inhibitory concentration (12.5 to 6.26 µg/mL), minimum bactericidal concentration (MBC) and anti-biofilm that showed a higher inhibitory effect of Cur-CLR-NE in compere with, free curcumin and clarithromycin against H. pylori. The in vivo results indicated that Cur-CLR-NE showed higher H. pylori clearance effect than free clarithromycin or curcumin under the same administration frequency and the same dose regimen. Histological analysis clearly showed that curcumin is highly effective in repairing damaged tissue. In addition, a potent synergistic effect was obvious between clarithromycin and curcumin in nano-emulsion system. The inflammation, superficial damage, the symptoms of gastritis including erosion in the mouse gastric mucosa, necrosis of the gastric epithelium gastric glands and interstitial oedema of tunica muscularis were observed in the positive control infected mice and absent from treated mice with Cur-CLR-NE.
Collapse
Affiliation(s)
- Farag M Mosallam
- Drug Radiation Research Department, Microbiology Lab, Biotechnology Division, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt.
| | - Mahmoud M Bendary
- Microbiology and Immunology Department, Faculty of pharmacy, Port-Said University, Port Fuad, Egypt
| | - Rana Elshimy
- Microbiology and immunology, Faculty of pharmacy, AL-Aharm Canadian University (ACU), Giza, Egypt
- Egyptian Drug Authority, EDA, Cairo, Egypt
| | - Ahmed I El-Batal
- Drug Radiation Research Department, Microbiology Lab, Biotechnology Division, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt
| |
Collapse
|
9
|
Jiang C, Zhang J, Wang W, Shan Z, Sun F, Tan Y, Tong Y, Qiu Y. Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets. Front Physiol 2023; 14:1158839. [PMID: 37664422 PMCID: PMC10469264 DOI: 10.3389/fphys.2023.1158839] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.
Collapse
Affiliation(s)
- Chengyao Jiang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Wentao Wang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Zexing Shan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Fan Sun
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yuen Tan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yilin Tong
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yue Qiu
- Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| |
Collapse
|
10
|
Ling LX, Ouyang Y, Hu Y. Research trends on nanomaterials in gastric cancer: a bibliometric analysis from 2004 to 2023. J Nanobiotechnology 2023; 21:248. [PMID: 37533041 PMCID: PMC10394877 DOI: 10.1186/s12951-023-02033-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 07/29/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Gastric cancer is one of the leading causes of cancer-related deaths worldwide. In recent years, an increasing number of studies aimed at designing and developing nanomaterials for use in diagnosing and treating gastric cancer have been conducted. In this study, we aimed to comprehensively assess the current status and trends of the research on the application of nanomaterials in gastric cancer through a bibliometric analysis. METHODS Studies focusing on nanomaterials and gastric cancer were retrieved from the Web of Science Core Collection database and relevant articles were selected for inclusion in the study according to the inclusion criteria. Bibliometric and visual analysis of the included publications was performed using VOSviewer and CiteSpace. RESULTS A total of 793 studies were included. An increase in annual publications was observed from 2004 to 2023. China, Iran and the USA were the dominant countries in this field, accounting for 66.1%, 11.5% and 7.2% of publications, respectively. Shanghai Jiao Tong University and Cui DX were the most influential institution and author, respectively. The International Journal of Nanomedicine was the most prolific journal; Biomaterials was the most cited and most cocited journal. Nanomaterial-related drug delivery and anticancer mechanisms were found to be the most widely researched aspects, and green synthesis and anticancer mechanisms are recent research hotspots. CONCLUSION In this study, we summarized the characteristics of publications and identified the most influential countries, institutions, authors, journals, hot topics and trends regarding the application of nanomaterials in gastric cancer.
Collapse
Affiliation(s)
- Li-Xiang Ling
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
| | - Yaobin Ouyang
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
- Department of Oncology, Mayo Clinic, Rochester, MN, USA
| | - Yi Hu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China.
- Department of Surgery at the Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin NT, Hong Kong, China.
| |
Collapse
|
11
|
Hu Q, Li Z, Li Y, Deng X, Chen Y, Ma X, Zeng J, Zhao Y. Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives. Phytother Res 2023. [PMID: 37157181 DOI: 10.1002/ptr.7866] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/17/2023] [Accepted: 04/25/2023] [Indexed: 05/10/2023]
Abstract
Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi-phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK-related signaling pathways, p53 signaling pathway, ER stress, Caspase-8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.
Collapse
Affiliation(s)
- Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Zhibei Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yubing Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xinyu Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuan Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
12
|
Luo Q, Liu N, Pu S, Zhuang Z, Gong H, Zhang D. A review on the research progress on non-pharmacological therapy of Helicobacter pylori. Front Microbiol 2023; 14:1134254. [PMID: 37007498 PMCID: PMC10063898 DOI: 10.3389/fmicb.2023.1134254] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 03/03/2023] [Indexed: 03/19/2023] Open
Abstract
Helicobacter pylori is a pathogenic microorganism that mainly resides in the human stomach and is the major cause of chronic gastritis, peptic ulcer and gastric cancer. Up to now, the treatment of Helicobacter pylori has been predominantly based on a combination of antibiotics and proton pump inhibitors. However, the increasing antibiotic resistance greatly limits the efficacy of anti-Helicobacter pylori treatment. Turning to non-antibiotic or non-pharmacological treatment is expected to solve this problem and may become a new strategy for treating Helicobacter pylori. In this review, we outline Helicobacter pylori's colonization and virulence mechanisms. Moreover, a series of non-pharmacological treatment methods for Helicobacter pylori and their mechanisms are carefully summarized, including probiotics, oxygen-rich environment or hyperbaric oxygen therapy, antibacterial photodynamic therapy, nanomaterials, antimicrobial peptide therapy, phage therapy and modified lysins. Finally, we provide a comprehensive overview of the challenges and perspectives in developing new medical technologies for treating Helicobacter pylori without drugs.
Collapse
Affiliation(s)
- Qian Luo
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Na Liu
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Sugui Pu
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Ze Zhuang
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Hang Gong
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
| | - Dekui Zhang
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China
- Key Laboratory of Digestive Diseases, LanZhou University Second Hospital, Lanzhou, China
| |
Collapse
|
13
|
Wang J, Du L, Chen X. Adenosine signaling: Optimal target for gastric cancer immunotherapy. Front Immunol 2022; 13:1027838. [PMID: 36189223 PMCID: PMC9523428 DOI: 10.3389/fimmu.2022.1027838] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/05/2022] [Indexed: 11/21/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignancy and leading cause of cancer-related deaths worldwide. Due to asymptomatic or only nonspecific early symptoms, GC patients are usually in the advanced stage at first diagnosis and miss the best opportunity of treatment. Immunotherapies, especially immune checkpoint inhibitors (ICIs), have dramatically changed the landscape of available treatment options for advanced-stage cancer patients. However, with regards to existing ICIs, the clinical benefit of monotherapy for advanced gastric cancer (AGC) is quite limited. Therefore, it is urgent to explore an optimal target for the treatment of GC. In this review, we summarize the expression profiles and prognostic value of 20 common immune checkpoint-related genes in GC from Gene Expression Profiling Interactive Analysis (GEPIA) database, and then find that the adenosinergic pathway plays an indispensable role in the occurrence and development of GC. Moreover, we discuss the pathophysiological function of adenosinergic pathway in cancers. The accumulation of extracellular adenosine inhibits the normal function of immune effector cells and facilitate the effect of immunosuppressive cells to foster GC cells proliferation and migration. Finally, we provide insights into potential clinical application of adenosinergic-targeting therapies for GC patients.
Collapse
Affiliation(s)
- Junqing Wang
- School of the 1St Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Linyong Du
- Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Xiangjian Chen, ; Linyong Du,
| | - Xiangjian Chen
- School of the 1St Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
- *Correspondence: Xiangjian Chen, ; Linyong Du,
| |
Collapse
|