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Ai Z, Liu B, Chen J, Zeng X, Wang K, Tao C, Chen J, Yang L, Ding Q, Zhou M. Advances in nano drug delivery systems for enhanced efficacy of emodin in cancer therapy. Int J Pharm X 2025; 9:100314. [PMID: 39834843 PMCID: PMC11743866 DOI: 10.1016/j.ijpx.2024.100314] [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: 11/06/2024] [Revised: 12/13/2024] [Accepted: 12/15/2024] [Indexed: 01/05/2025] Open
Abstract
Cancer remains one of the leading causes of death worldwide, highlighting the urgent need for novel antitumor drugs. Natural products have long been a crucial source of anticancer agents. Among these, emodin (EMO), a multifunctional anthraquinone compound, exhibits significant anticancer effects but is hindered in clinical applications by challenges such as low solubility, rapid metabolism, poor bioavailability, and off-target toxicity. Nano drug delivery systems offer effective strategies to overcome these limitations by enhancing the solubility, stability, bioavailability, and targeting ability of EMO. While substantial progress has been made in developing EMO-loaded nanoformulations, a comprehensive review on this topic is still lacking. This paper aims to fill this gap by providing an overview of recent advancements in nanocarriers for EMO delivery and their anticancer applications. These carriers include liposomes, nanoparticles, polymeric micelles, nanogels, and others, with nanoparticle-based formulations being the most extensively explored. Nanoformulations encapsulating EMO have demonstrated promising therapeutic results against various cancers, particularly breast cancer, followed by liver and lung cancers. We systematically summarize the preparation methods, materials, and physicochemical properties of EMO-loaded nanopreparations, underscoring key findings on how nanotechnology improves the anticancer efficacy of EMO. This review provides valuable insights for researchers engaged in developing nano delivery systems for anticancer drugs.
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Affiliation(s)
- Zhenghao Ai
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Bingyao Liu
- Department of Radiology, West China Hospital Sichuan University Jintang Hospital, Chengdu, China
| | - Junyan Chen
- Department of Cardiothoracic Surgery, Luzhou People's Hospital, Luzhou, China
| | - Xinhao Zeng
- Department of Pediatric Surgery, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, China
| | - Ke Wang
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Chao Tao
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Jing Chen
- Department of Clinical Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China
| | - Liuxuan Yang
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Qian Ding
- Department of Clinical Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China
| | - Meiling Zhou
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
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Xu P, Xu K, Li J, Liu A, Xiao W, Sun L. Screening and preparation of curcumin nano-formulations combined with dissolving microneedles on the application in the effective treatment of psoriasis. Int J Pharm 2025; 675:125528. [PMID: 40157563 DOI: 10.1016/j.ijpharm.2025.125528] [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: 01/15/2025] [Revised: 02/20/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Psoriasis, a prevalent immunoinflammatory skin condition, is characterized by abnormal skin thickening, which complicates traditional topical drug delivery and hinders drug penetration. Our goal is to enhance the efficacy of psoriasis treatment by developing a transdermal drug formulation. Microneedles (MNs) can improve treatment outcomes by increasing the absorption of topical medications through skin penetration. Curcumin (Cur), a natural anti-inflammatory, antioxidant, and immunomodulatory small molecule with water-insoluble properties, shows promise for psoriasis relief. In this research, three Cur nano-formulations (NFs) were screened and prepared using antisolvent and ethanol injection methods, with one being dispersed into hyaluronic acid (HA) dissolving MNs. A transdermal nano-MNs delivery system was constructed using a double-layer centrifugation technique. This co-delivery system overcame Cur's solubility issues, poor absorption, and instability, allowing targeted and efficient delivery of Cur-NFs to the skin without being hindered by the skin barrier. In vitro studies demonstrated that Cur-NF dissolving MNs possess adequate mechanical properties for skin implantation, exhibit rapid dissolution, and achieve an effective drug release rate of 73 % within 6 h. Pharmacodynamic evaluations demonstrated that the MNs system effectively ameliorated key psoriatic skin manifestations. Notably, MNs treatment significantly reduced the Psoriasis Area and Severity Index (PASI) score from 12.0 ± 0.0 (model group) to 4.7 ± 0.5 (p < 0.05), alongside a marked suppression of pro-inflammatory cytokines, including TNF-α, IL-17, IL-22, and IL-23, compared to untreated psoriatic controls. Therefore, the composite dissolving MNs delivery system loaded with Cur-NFs represents a promising approach for psoriasis treatment.
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Affiliation(s)
- Peng Xu
- Department of Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China; Department of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Kun Xu
- Department of Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China
| | - Jiayin Li
- Department of Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China
| | - Aoxue Liu
- Department of Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China
| | - Wei Xiao
- Department of Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China
| | - Lin Sun
- Department of Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China.
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Guo Z, Zheng H, Wang T, Han N, Zhang H, Li J, Cheng X, Ye J, Du S, Li P. Combination Nanodrug Delivery Systems Facilitate the Syncretism of Chemotherapy with Immunotherapy to Promote Cancer Treatment. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2405752. [PMID: 39544164 DOI: 10.1002/smll.202405752] [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: 07/10/2024] [Revised: 10/12/2024] [Indexed: 11/17/2024]
Abstract
Cancer has emerged as a significant threat that gravely endanger human health. Anti-tumor immunotherapy has now emerged as an important treatment for cancer. However, immunosuppressive tumor microenvironment limits the antitumor immunity. The importance of the immune system in the cancer treatment process must be emphasized. Herein, two precision-targeted nanoparticles PD-L1@Cur-NPs and PD-1@AS-NPs are constructed for cancer treatment. PD-L1@Cur-NPs can precisely target tumor cells in vivo to eradicate tumor cells or induce them apoptosis. PD-1@AS-NPs can precisely target T cells in vivo to activate the T cell-mediated immune system and induce antitumor immune responses. Furthermore, these two nanoparticles have good synergistic effect and show stronger antitumor effect after combination. After treatment with the combination of two nanoparticles, the tumor volumes of C57BL/6 tumor-bearing mice are significantly reduced. Moreover, the percentage of CD8+T cells and CD4+T cells in the tumor significantly increased, and the percentage of regulatory T cells significantly decreased. The percentage of memory T cells and memory effector T cells in the spleen also significantly increased after treatment, suggesting that the antitumor immunity is activated after treatment. This study provides a new antitumor treatment strategy combining chemotherapy and immunotherapy, which has good application prospect.
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Affiliation(s)
- Zishuo Guo
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Haocheng Zheng
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Tieshan Wang
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Ning Han
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Haitong Zhang
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Jialing Li
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Xuehao Cheng
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Jinhong Ye
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Shouying Du
- Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Pengyue Li
- Beijing University of Chinese Medicine, Beijing, 102488, China
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Rezagholizade-shirvan A, Soltani M, Shokri S, Radfar R, Arab M, Shamloo E. Bioactive compound encapsulation: Characteristics, applications in food systems, and implications for human health. Food Chem X 2024; 24:101953. [PMID: 39582652 PMCID: PMC11584689 DOI: 10.1016/j.fochx.2024.101953] [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: 09/26/2024] [Revised: 10/28/2024] [Accepted: 10/30/2024] [Indexed: 11/26/2024] Open
Abstract
Nanotechnology plays a pivotal role in food science, particularly in the nanoencapsulation of bioactive compounds, to enhance their stability, bioavailability, and therapeutic potential. This review aims to provide a comprehensive analysis of the encapsulation of bioactive compounds, emphasizing the characteristics, food applications, and implications for human health. This work offers a detailed comparison of polymers such as sodium alginate, gum Arabic, chitosan, cellulose, pectin, shellac, and xanthan gum, while also examining both conventional and emerging encapsulation techniques, including freeze-drying, spray-drying, extrusion, coacervation, and supercritical anti-solvent drying. The contribution of this review lies in highlighting the role of encapsulation in improving system stability, controlling release rates, maintaining bioactivity under extreme conditions, and reducing lipid oxidation. Furthermore, it explores recent technological advances aimed at optimizing encapsulation processes for targeted therapies and functional foods. The findings underline the significant potential of encapsulation not only in food supplements and functional foods but also in supportive medical treatments, showcasing its relevance to improving human health in various contexts.
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Affiliation(s)
| | - Mahya Soltani
- Student Research Committee, Department of Food Science and Technology, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Samira Shokri
- Nutritional Health Research Center, Lorestan University of Medical Sciences, Lorestan, Iran
| | - Ramin Radfar
- Department of Agriculture and Food Policies, Agricultural Planning, Economic and Rural Development Research Institute (APERDRI), Tehran, Iran
| | - Masoumeh Arab
- Department of Food Science and Technology, School of Public Health, Shahid sadoughi University of Medical Sciences, Yazd, Iran Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ehsan Shamloo
- Department of Food Science and Technology, Neyshabur University of Medical Sciences, Neyshabur, Iran
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Rai M, Ingle AP, Törős G, Prokisch J. Assessing the efficacy of carbon nanodots derived from curcumin on infectious diseases. Expert Rev Anti Infect Ther 2024; 22:1107-1121. [PMID: 39317385 DOI: 10.1080/14787210.2024.2409401] [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: 05/01/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 09/26/2024]
Abstract
INTRODUCTION The threat of new, emerging, and multidrug-resistant microbes is increasing which has created the necessity for new antimicrobials. In this regard, nanotechnology can be an alternative for the treatment of infectious microbes. Curcumin has been used since ancient times as antimicrobials; however, it has limitations due to its less aqueous solubility, bioavailability, and biocompatibility. This problem can be solved by curcumin-derived carbon nanodots, which are emerging antimicrobials of <10 nm size, water-soluble, biocompatible, less toxic, and fluorescent. AREAS COVERED The review discusses the application of curcumin-derived carbon nanodots against various pathogenic microbes including bacteria and dreaded viruses like SARS-CoV-2. In addition, the role of curcumin carbon nanodots in biolabelling of pathogenic microbes, mechanism of action, bioimaging, and therapy has been critically examined. EXPERT OPINION Carbon nanodots play an important role in combating pathogenic microbes by early diagnosis, bioimaging, nanocarrier for antimicrobial drugs, and therapy of infectious diseases. Curcumin carbon nanodots have already demonstrated their benefits of being water soluble, bioavailable, and biocompatible. However, more thorough research is needed to understand the efficacy and safety of curcumin carbon nanodots. In the future, curcumin-derived carbon nanodots can be used as alternative antimicrobial agents to fight microbial infections including multidrug-resistant microbes.
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Affiliation(s)
- Mahendra Rai
- Department of Biotechnology, Sant Gadge Baba Amravati University, Amravati, India
- Institute of Animal Science, Biotechnology and Nature Conservation, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Debrecen, Hungary
| | - Avinash P Ingle
- Biotechnology Centre, Department of Agricultural Botany, Dr. PDKV, Akola, India
| | - Gréta Törős
- Institute of Animal Science, Biotechnology and Nature Conservation, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Debrecen, Hungary
- School of Animal Husbandry, University of Debrecen, Debrecen, Hungary
| | - József Prokisch
- Institute of Animal Science, Biotechnology and Nature Conservation, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Debrecen, Hungary
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Golmohammadi M, Zamanian MY, Al‐Ani AM, Jabbar TL, Kareem AK, Aghaei ZH, Tahernia H, Hjazi A, Jissir SA, Hakimizadeh E. Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review. Animal Model Exp Med 2024; 7:853-867. [PMID: 39219410 PMCID: PMC11680487 DOI: 10.1002/ame2.12491] [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: 06/15/2024] [Accepted: 08/10/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Breast cancer (BC) continues to be a significant global health issue, with a rising number of cases requiring ongoing research and innovation in treatment strategies. Curcumin (CUR), a natural compound derived from Curcuma longa, and similar compounds have shown potential in targeting the STAT3 signaling pathway, which plays a crucial role in BC progression. AIMS The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms. MATERIALS & METHODS The literature search conducted for this study involved utilizing the Scopus, ScienceDirect, PubMed, and Google Scholar databases in order to identify pertinent articles. RESULTS This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation, thereby suppressing the proliferation of cancer cells, inducing apoptosis, and inhibiting metastasis. The review demonstrates that CUR directly inhibits the phosphorylation of STAT3, preventing its movement into the nucleus and its ability to bind to DNA, thereby hindering the survival and proliferation of cancer cells. CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages (TAMs). CUR analogues, such as hydrazinocurcumin (HC), FLLL11, FLLL12, and GO-Y030, show improved bioavailability and potency in inhibiting STAT3, resulting in reduced cell proliferation and increased apoptosis. CONCLUSION CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway. These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.
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Affiliation(s)
| | - Mohammad Yassin Zamanian
- Department of Physiology, School of MedicineHamadan University of Medical SciencesHamadanIran
- Department of Pharmacology and Toxicology, School of PharmacyHamadan University of Medical SciencesHamadanIran
| | - Ahmed Muzahem Al‐Ani
- Department of Medical Laboratories TechnologyAL‐Nisour University CollegeBaghdadIraq
| | | | - Ali Kamil Kareem
- Biomedical Engineering DepartmentAl‐Mustaqbal University CollegeHillahIraq
| | - Zeinab Hashem Aghaei
- Preventative Gynecology Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Hossein Tahernia
- Molecular Medicine Research Center, Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran
| | - Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical SciencesPrince Sattam bin Abdulaziz UniversityAl‐KharjSaudi Arabia
| | | | - Elham Hakimizadeh
- Physiology‐Pharmacology Research Center, Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran
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Liu CJ, Lin JH, Li MT, Cho EC, Lee KC. Post-therapy via integrated curcumin and doxorubicin modified cerium-based UiO-66 MOFs using an antioxidant and anticancer therapeutic strategy. J Mater Chem B 2024; 12:11983-11995. [PMID: 39440435 DOI: 10.1039/d4tb01206b] [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: 10/25/2024]
Abstract
The quest for effective cancer treatment methodologies underpins numerous research endeavors. Despite the therapeutic efficacy of conventional chemotherapy against malignant tumors, tumor recurrence post-therapy remains a formidable challenge. Addressing this, we developed a dual drug delivery system, rooted in a modified metal-organic framework (MOF), specifically by substituting the metal nodes of Uio-66 with cerium to augment its anti-oxidative potential. This engineered system, pyrene-modified hyaluronic acid, functions as a linker, enabling the self-assembly and encapsulation of both the material and the therapeutic agents, and encompasses both doxorubicin and curcumin, aimed at targeting cancer cell eradication and tumorigenesis inhibition. This system demonstrated significant antioxidant capacity through free radical scavenging assays, positioning it as a potential agent in mitigating tumor recurrence. Enhanced anti-tumor activity was distinctly evidenced in human colon cancer cell lines. Additionally, in vitro drug release assessments revealed slow-release kinetics and acid-responsive traits, attributed to the incorporation of pyrenylated hyaluronic acid. Within the xenograft nude mouse model, this system contained a lower amount of doxorubicin, yet, exhibited tumor inhibition capability comparable to the free doxorubicin group. Moreover, it delivered anticancer efficiency under conditions of enhanced antioxidative capacity, underscoring its prospective utility in clinical cancer therapeutics. This dual drug delivery platform not only advances cancer treatment and prophylaxis but also extends novel insights into the therapeutic implications of simultaneous dual drug delivery systems.
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Affiliation(s)
- Chao-Jan Liu
- Department of Science Education, National Taipei University of Education, No. 134, Sect. 2, Heping E. Rd., Da'an District, Taipei City 106, Taiwan.
| | - Jung-Hua Lin
- Department of Science Education, National Taipei University of Education, No. 134, Sect. 2, Heping E. Rd., Da'an District, Taipei City 106, Taiwan.
| | - Man-Tzu Li
- Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City, 110, Taiwan.
| | - Er-Chieh Cho
- Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City, 110, Taiwan.
- School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City, 110, Taiwan
- Cancer Center, Wan Fang Hospital, Taipei Medical University, 110, Taiwan
- TMU Research Center of Cancer Translational Medicine, Taiwan
| | - Kuen-Chan Lee
- Department of Science Education, National Taipei University of Education, No. 134, Sect. 2, Heping E. Rd., Da'an District, Taipei City 106, Taiwan.
- Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei City, 110, Taiwan
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Torres Fredes IP, Cortés-Adasme EN, Barrientos BA, Real JP, Gomez CG, Palma SD, Kogan MJ, Real DA. 3D-Printed Plasmonic Nanocomposites: VAT Photopolymerization for Photothermal-Controlled Drug Release. Pharmaceuticals (Basel) 2024; 17:1453. [PMID: 39598365 PMCID: PMC11597631 DOI: 10.3390/ph17111453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/11/2024] [Accepted: 10/14/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Gold nanoparticles can generate heat upon exposure to radiation due to their plasmonic properties, which depend on particle size and shape. This enables precise control over the release of active substances from polymeric pharmaceutical formulations, minimizing side effects and premature release. The technology of 3D printing, especially vat photopolymerization, is valuable for integrating nanoparticles into complex formulations. METHOD This study aimed to incorporate gold nanospheres (AuNSs) and nanorods (AuNRs) into polymeric matrices using vat photopolymerization, allowing for controlled drug release with exposure to 532 nm and 1064 nm wavelengths. RESULTS The AuNSs (27 nm) responded to 532 nm and the NRs (60 nm length, 10 nm width) responded to 1064 nm. Niclosamide was used as the drug model. Ternary blends of Polyethylene Glycol Diacrylate 250 (PEGDA 250), Polyethylene Glycol 400 (PEG 400), and water were optimized using DesignExpert 11 software for controlled drug release upon specific wavelength exposure. Three matrices, selected based on solubility and printability, underwent rigorous characterization. Two materials achieved controlled drug release with specific wavelengths. Bilayer devices combining AuNSs and AuNRs demonstrated selective drug release based on irradiation wavelength. CONCLUSIONS A pharmaceutical device was developed, capable of controlling drug release upon irradiation, with potential applications in treatments requiring delayed administration.
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Affiliation(s)
- Ignacia Paz Torres Fredes
- Department of Pharmacological and Toxicological Chemistry, University of Chile, Santos Dumont 964, Santiago 8380494, Chile; (I.P.T.F.); (E.N.C.-A.)
- Advanced Center of Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, IndePendencia, Santiago 8380494, Chile
| | - Elizabeth Nicole Cortés-Adasme
- Department of Pharmacological and Toxicological Chemistry, University of Chile, Santos Dumont 964, Santiago 8380494, Chile; (I.P.T.F.); (E.N.C.-A.)
- Advanced Center of Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, IndePendencia, Santiago 8380494, Chile
| | - Bruno Andrés Barrientos
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA-CONICET), Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina; (B.A.B.); (J.P.R.); (S.D.P.)
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina
| | - Juan Pablo Real
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA-CONICET), Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina; (B.A.B.); (J.P.R.); (S.D.P.)
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina
| | - Cesar Gerardo Gomez
- Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000XHUA, Argentina;
- Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina
| | - Santiago Daniel Palma
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA-CONICET), Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina; (B.A.B.); (J.P.R.); (S.D.P.)
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina
| | - Marcelo Javier Kogan
- Department of Pharmacological and Toxicological Chemistry, University of Chile, Santos Dumont 964, Santiago 8380494, Chile; (I.P.T.F.); (E.N.C.-A.)
- Advanced Center of Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, IndePendencia, Santiago 8380494, Chile
| | - Daniel Andrés Real
- Department of Pharmacological and Toxicological Chemistry, University of Chile, Santos Dumont 964, Santiago 8380494, Chile; (I.P.T.F.); (E.N.C.-A.)
- Advanced Center of Chronic Diseases (ACCDiS), Universidad de Chile, Santos Dumont 964, IndePendencia, Santiago 8380494, Chile
- Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA-CONICET), Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina; (B.A.B.); (J.P.R.); (S.D.P.)
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Córdoba X5000XHUA, Argentina
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Liang J, Liang Y, Yan F, Zhang M, Wu W. Novel targeting liposomes with enhanced endosomal escape for co-delivery of doxorubicin and curcumin. Colloids Surf B Biointerfaces 2024; 245:114267. [PMID: 39326226 DOI: 10.1016/j.colsurfb.2024.114267] [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: 08/07/2024] [Revised: 09/15/2024] [Accepted: 09/23/2024] [Indexed: 09/28/2024]
Abstract
Effective endosomal escape is crucial for enhancing the efficiency of nanodrug delivery systems. In this study, we developed a novel liposomal system utilizing acid-sensitive N-(3-amino-propyl) imidazole cholesterol (IM-Chol), specifically designed for the targeted co-delivery of doxorubicin (DOX) and curcumin (CUR) to hepatocellular carcinoma (HCC). Designated as GA-IM-LIP@DOX/CUR, this liposomal system incorporates glycyrrhetinic acid (GA) to improve target specificity toward HCC cells. Notably, both drugs exhibited pH-sensitive release profiles, facilitating precise drug release within acidic environments. Our investigation into cellular uptake demonstrated that modified liposomes, GA-IM-LIP@FITC and IM-LIP@FITC, achieved progressively enhanced intracellular accumulation of FITC compared to unmodified liposomes. Competitive inhibition assays utilizing free GA further validated the targeting efficacy of GA. Moreover, the GA-IM-LIP@FITC and IM-LIP@FITC groups exhibited rapid endosomal escape of FITC within the first two hours, in contrast to delayed escape observed in the LIP@FITC group, confirming that the protonation of IM-Chol promotes drug release into the cytosol. In vivo studies substantiated that GA-IM-LIP@DOX/CUR effectively inhibited tumor growth. This research provides significant insights into the design and functionality of the GA-IM-LIP@DOX/CUR liposomal system, underscoring its potential to enhance drug delivery strategies in the treatment of HCC.
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Affiliation(s)
- Ju Liang
- School of Chemistry and Chemical Engineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Ying Liang
- School of Chemistry and Chemical Engineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Fuqing Yan
- School of Chemistry and Chemical Engineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Mengyi Zhang
- School of Chemistry and Chemical Engineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Wenlan Wu
- School of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, China.
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10
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Fakhri S, Moradi SZ, Moradi SY, Piri S, Shiri Varnamkhasti B, Piri S, Khirehgesh MR, Bishayee A, Casarcia N, Bishayee A. Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway. BMC Cancer 2024; 24:1079. [PMID: 39223494 PMCID: PMC11368033 DOI: 10.1186/s12885-024-12715-7] [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: 03/12/2024] [Accepted: 07/26/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Due to the complex pathophysiological mechanisms involved in cancer progression and metastasis, current therapeutic approaches lack efficacy and have significant adverse effects. Therefore, it is essential to establish novel strategies for combating cancer. Phytochemicals, which possess multiple biological activities, such as antioxidant, anti-inflammatory, antimutagenic, immunomodulatory, antiproliferative, anti-angiogenesis, and antimetastatic properties, can regulate cancer progression and interfere in various stages of cancer development by suppressing various signaling pathways. METHODS The current systematic and comprehensive review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria, using electronic databases, including PubMed, Scopus, and Science Direct, until the end of December 2023. After excluding unrelated articles, 111 related articles were included in this systematic review. RESULTS In this current review, the major signaling pathways of cancer metabolism are highlighted with the promising anticancer role of phytochemicals. This was through their ability to regulate the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) signaling pathway. The AMPK/PGC-1α signaling pathway plays a crucial role in cancer cell metabolism via targeting energy homeostasis and mitochondria biogenesis, glucose oxidation, and fatty acid oxidation, thereby generating ATP for cell growth. As a result, targeting this signaling pathway may represent a novel approach to cancer treatment. Accordingly, alkaloids, phenolic compounds, terpene/terpenoids, and miscellaneous phytochemicals have been introduced as promising anticancer agents by regulating the AMPK/PGC-1α signaling pathway. Novel delivery systems of phytochemicals targeting the AMPK/PGC-1α pathway in combating cancer are also highlighted in this review.
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Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.
| | - Seyed Zachariah Moradi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Seyed Yahya Moradi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Sarina Piri
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Behrang Shiri Varnamkhasti
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Sana Piri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Mohammad Reza Khirehgesh
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | | | - Nicolette Casarcia
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA
| | - Anupam Bishayee
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
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Mukkavilli V, Ramakrishnan G, Gujjula KR, S B, Chamarthy S, Mekala JR. Molecular Understanding and Pharmacological Potency of Plant-Derived Compounds in Colorectal Cancer (CRC): A Critical Analysis and Future Perspectives. Cell Biochem Biophys 2024; 82:1777-1795. [PMID: 38965179 DOI: 10.1007/s12013-024-01370-1] [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] [Accepted: 06/13/2024] [Indexed: 07/06/2024]
Abstract
Colorectal cancer (CRC) is the main driver of fatality and the 3rd most often determined malignancy. Despite advances in detection and therapy, colorectal cancer (CRC) endures as the largest driver of cancer-related morbidity, and mortality. Modern habits and dietary negligence might be one of the reasons that have enhanced cancer prevalence. Thus, changes in Dietary habits will have a better impact, and help in finding a better cure for CRC. Initially, CRC was explored as a genetic event and currently, the research is focused on the epigenetic modifications of chromatin and microRNA (miRNA) in CRC cells. Natural products such as Curcumin, Resveratrol, Flavonoids, and Ellagitannins are been explored as compounds from the perspective of genetic, epigenetic, and miRNA modifications which will have future therapeutic aspects. Also, the extracts of these key players and their analogs will intervene the signaling pathway activation that involves in cancer propagation, apoptosis, cell cycle arrest, and epigenetic and miRNA modifications. Modulations of these miRNAs, and modification globally might have impact on CRC progression, and cancer tumor cell sensitivity.
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Affiliation(s)
- Vaagdevi Mukkavilli
- Department of Biotechnology, Koneru Lakshmaiah Education Foundation (Deemed to be University), Green Fields, 522502, Vaddeswram, AP, India
| | - Gnanasekaran Ramakrishnan
- Department of Biotechnology, Koneru Lakshmaiah Education Foundation (Deemed to be University), Green Fields, 522502, Vaddeswram, AP, India.
| | - Koteswara Reddy Gujjula
- Department of Biotechnology, Koneru Lakshmaiah Education Foundation (Deemed to be University), Green Fields, 522502, Vaddeswram, AP, India
| | - Balachandran S
- Dept of Chemical Engineering, Saveetha Engineering College, Saveetha Nagar Thandalam, 602105, Chennai, Tamil Nadu, India
| | - Sahiti Chamarthy
- Department of Biotechnology, Koneru Lakshmaiah Education Foundation (Deemed to be University), Green Fields, 522502, Vaddeswram, AP, India
| | - Janaki Ramaiah Mekala
- Department of Biotechnology, Koneru Lakshmaiah Education Foundation (Deemed to be University), Green Fields, 522502, Vaddeswram, AP, India.
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Hendel N, Sarri D, Sarri M, Napoli E, Palumbo Piccionello A, Ruberto G. Phytochemical Analysis and Antioxidant and Antifungal Activities of Powders, Methanol Extracts, and Essential Oils from Rosmarinus officinalis L. and Thymus ciliatus Desf. Benth. Int J Mol Sci 2024; 25:7989. [PMID: 39063231 PMCID: PMC11276860 DOI: 10.3390/ijms25147989] [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: 05/16/2024] [Revised: 07/05/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Chemical residues in food pose health risks such as cancer and liver issues. This has driven the search for safer natural alternatives to synthetic fungicides and preservatives. The aim of this study was to characterize the chemical composition of the essential oils (EO), determine the polyphenolic contents, and evaluate the in vitro antioxidant and antifungal activities of methanol extracts (ME), essential oils (EO), and powders from Rosmarinus officinalis L. (rosemary) and Thymus ciliatus (Desf) Benth. (thyme) from the M'sila region, Algeria. The chemical composition of the EOs was determined by GC-MS. R. officinalis EO was composed of 31 components, mainly camphor (41.22%), camphene (18.14%), and α-pinene (17.49%); T. ciliatus EO was composed of 58 components, mainly, in percentage, α-pinene (22.18), myrcene (13.13), β-pinene (7.73), β-caryophyllene (10.21), and germacrene D (9.90). The total phenols and flavonoids were determined spectrophotometrically, and the rosemary ME was found to possess the highest polyphenolic content (127.1 ± 2.40 µg GAE/mg), while the thyme ME had the highest flavonoid content (48.01 ± 0.99 µg QE/mg). The antioxidant activity was assessed using three methods: rosemary ME was the most potent, followed by DPPH (IC50 = 13.43 ± 0.14 µg/mL), β-carotene/linoleic acid (IC50 = 39.01 ± 2.16 μg/mL), and reducing power (EC50 = 15.03 ± 1.43 µg/mL). Antifungal activity was assessed for 32 pathogenic and foodborne fungi. Four methods were applied to the solid medium. Incorporating the powdered plant into the culture medium (at 10%) reduced the fungal growth to greater than 50% in 21.88% and 6.25% of all fungal isolates, for R. officinalis and T. ciliatus, respectively. The ME, applied by the well diffusion method (0.1 g/mL), was less effective. Different concentrations of EO were tested. Incorporating the EO into the culture medium (1500 μL/L) inhibited 50% of the molds to levels of 50 and 75% for R. officinalis and T. ciliatus, respectively, with the complete inhibition of four fungi. Fumigated EO (15 μL) inhibited 65% of the molds to levels of 65 and 81.25% for R. officinalis and T. ciliatus, respectively, with the complete inhibition of five fungi. There was little to no sporulation in conjunction with the inhibition. Our results revealed some of the potential of the studied plants to fight foodborne molds and presented their promising characteristics as a source of alternatives to chemical pesticides and synthetic preservatives. Further studies are needed to find adequate application techniques in the food safety area.
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Affiliation(s)
- Noui Hendel
- Department of Microbiology and Biochemistry, Faculty of Sciences, University Mohamed Boudiaf of M’sila, M’sila 28000, Algeria
- Laboratory of Biology: Applications in Health and Environment, University of M’sila, M’sila 28000, Algeria
| | - Djamel Sarri
- Department of Nature and Life Sciences, Faculty of Sciences, University Mohamed Boudiaf of M’sila, M’sila 28000, Algeria; (D.S.); (M.S.)
| | - Madani Sarri
- Department of Nature and Life Sciences, Faculty of Sciences, University Mohamed Boudiaf of M’sila, M’sila 28000, Algeria; (D.S.); (M.S.)
| | - Edoardo Napoli
- Institute of Biomolecular Chemistry, National Research Council ICB-CNR, 95126 Catania, Italy; (E.N.); (G.R.)
| | - Antonio Palumbo Piccionello
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche-STEBICEF, Università degli Studi di Palermo, Viale delle Scienze Ed. 17, 90128 Palermo, Italy;
| | - Giuseppe Ruberto
- Institute of Biomolecular Chemistry, National Research Council ICB-CNR, 95126 Catania, Italy; (E.N.); (G.R.)
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Kaveh Zenjanab M, Hashemzadeh N, Alimohammadvand S, Sharifi-Azad M, Dalir Abdolahinia E, Jahanban-Esfahlan R. Notch Signaling Suppression by Golden Phytochemicals: Potential for Cancer Therapy. Adv Pharm Bull 2024; 14:302-313. [PMID: 39206407 PMCID: PMC11347744 DOI: 10.34172/apb.2024.035] [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: 09/14/2023] [Revised: 01/09/2024] [Accepted: 03/03/2024] [Indexed: 09/04/2024] Open
Abstract
Cancer is one of the main causes of mortality worldwide. Cancer cells are characterized by unregulated cellular processes, including proliferation, progression, and angiogenesis. The occurrence of these processes is due to the dysregulation of various signaling pathways such as NF-κB (nuclear factor-κB), Wnt/beta-catenin, Notch signaling and MAPK (mitogen-activated protein kinases). Notch signaling pathways cause the progression of various types of malignant tumors. Among the phytochemicals for cancer therapy, several have attracted great interest, including curcumin, genistein, quercetin, silibinin, resveratrol, cucurbitacin and glycyrrhizin. Given the great cellular and molecular heterogeneity within tumors and the high toxicity and side effects of synthetic chemotherapeutics, natural products with pleiotropic effects that simultaneously target numerous signaling pathways appear to be ideal substitutes for cancer therapy. With this in mind, we take a look at the current status, impact and potential of known compounds as golden phytochemicals on key signaling pathways in tumors, focusing on the Notch pathway. This review may be useful for discovering new molecular targets for safe and efficient cancer therapy with natural chemotherapeutics.
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Affiliation(s)
| | - Nastaran Hashemzadeh
- Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sajjad Alimohammadvand
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoumeh Sharifi-Azad
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elaheh Dalir Abdolahinia
- Department of Oral Science and Translation Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33314, US
| | - Rana Jahanban-Esfahlan
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Zhang Y, Chen Y, Liu H, Sun B. Advances of nanoparticle derived from food in the control of α-dicarbonyl compounds-A review. Food Chem 2024; 444:138660. [PMID: 38330613 DOI: 10.1016/j.foodchem.2024.138660] [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: 10/17/2023] [Revised: 01/04/2024] [Accepted: 01/31/2024] [Indexed: 02/10/2024]
Abstract
α-Dicarbonyl compounds (α-DCs) are predominantly generated through the thermal processing of carbohydrate and protein-rich food. They are pivotal precursors to hazard formation, such as advanced glycation end products (AGEs), acrylamide, and furan. Their accumulation within the body will be genotoxicity and neurotoxicity. Recently, significant advancements have been made in nanotechnology, leading to the widespread utilization of nanomaterials as functional components in addressing the detrimental impact of α-DCs. This review focuses on the control of α-DCs through the utilization of nanoparticle-based functional factors, which were prepared by using edible components as resources. Four emerging nanoparticles are introduced including phenolic compounds-derived nanoparticle, plant-derived nanoparticle, active peptides-derived nanoparticle, and functional minerals-derived nanoparticle. The general control mechanisms as well as the recent evidence pertaining to the aforementioned aspects were also discussed, hoping to valuable helpful references for the development of innovative α-DCs scavengers and identifying the further scope of research.
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Affiliation(s)
- Ying Zhang
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing Technology and Business University, No. 11 Fucheng Road, Beijing 100048, People's Republic of China
| | - Yunhai Chen
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing Technology and Business University, No. 11 Fucheng Road, Beijing 100048, People's Republic of China
| | - Huilin Liu
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing Technology and Business University, No. 11 Fucheng Road, Beijing 100048, People's Republic of China.
| | - Baoguo Sun
- Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing Technology and Business University, No. 11 Fucheng Road, Beijing 100048, People's Republic of China
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15
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Liu S, Tian H, Ming H, Zhang T, Gao Y, Liu R, Chen L, Yang C, Nice EC, Huang C, Bao J, Gao W, Shi Z. Mitochondrial-Targeted CS@KET/P780 Nanoplatform for Site-Specific Delivery and High-Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2308027. [PMID: 38308137 PMCID: PMC11005749 DOI: 10.1002/advs.202308027] [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: 10/24/2023] [Revised: 01/07/2024] [Indexed: 02/04/2024]
Abstract
Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it is imperative to develop novel, potent therapeutic modalities. Ketoconazole (KET) has shown excellent therapeutic efficacy against HCC by eliciting apoptosis. However, its limited water solubility hampers its application in clinical treatment. Herein, a mitochondria-targeted chemo-photodynamic nanoplatform, CS@KET/P780 NPs, is designed using a nanoprecipitation strategy by integrating a newly synthesized mitochondria-targeted photosensitizer (P780) and chemotherapeutic agent KET coated with chondroitin sulfate (CS) to amplify HCC therapy. In this nanoplatform, CS confers tumor-targeted and subsequently pH-responsive drug delivery behavior by binding to glycoprotein CD44, leading to the release of P780 and KET. Mechanistically, following laser irradiation, P780 targets and destroys mitochondrial integrity, thus inducing apoptosis through the enhancement of reactive oxygen species (ROS) buildup. Meanwhile, KET-induced apoptosis synergistically enhances the anticancer effect of P780. In addition, tumor cells undergoing apoptosis can trigger immunogenic cell death (ICD) and a longer-term antitumor response by releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), which together contribute to improved therapeutic outcomes in HCC. Taken together, CS@KET/P780 NPs improve the bioavailability of KET and exhibit excellent therapeutic efficacy against HCC by exerting chemophototherapy and antitumor immunity.
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Affiliation(s)
- Shanshan Liu
- Clinical Medical CollegeAffiliated Hospital of Chengdu UniversityChengdu UniversityChengdu610106China
- Department of Clinical PharmacySchool of PharmacyZunyi Medical UniversityZunyi563006China
| | - Hailong Tian
- State Key Laboratory of Biotherapy and Cancer CenterWest China Hospitaland West China School of Basic Medical Sciences & Forensic MedicineSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu610041China
| | - Hui Ming
- State Key Laboratory of Biotherapy and Cancer CenterWest China Hospitaland West China School of Basic Medical Sciences & Forensic MedicineSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu610041China
| | - Tingting Zhang
- State Key Laboratory of Biotherapy and Cancer CenterWest China Hospitaland West China School of Basic Medical Sciences & Forensic MedicineSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu610041China
| | - Yajie Gao
- The First Affiliated Hospital of Ningbo UniversityNingbo315020China
| | - Ruolan Liu
- School of Basic Medical SciencesChengdu University of Traditional Chinese MedicineChengdu611137China
| | - Lihua Chen
- School of Basic Medical SciencesChengdu University of Traditional Chinese MedicineChengdu611137China
| | - Chen Yang
- School of Basic Medical SciencesChengdu University of Traditional Chinese MedicineChengdu611137China
| | - Edouard C. Nice
- Department of Biochemistry and Molecular BiologyMonash UniversityClaytonVIC3800Australia
| | - Canhua Huang
- State Key Laboratory of Biotherapy and Cancer CenterWest China Hospitaland West China School of Basic Medical Sciences & Forensic MedicineSichuan UniversityCollaborative Innovation Center for BiotherapyChengdu610041China
| | - Jinku Bao
- College of Life SciencesSichuan UniversityChengdu610064China
| | - Wei Gao
- Clinical Medical CollegeAffiliated Hospital of Chengdu UniversityChengdu UniversityChengdu610106China
- Clinical Genetics LaboratoryAffiliated Hospital & Clinical Medical College of Chengdu UniversityChengdu610081China
| | - Zheng Shi
- Clinical Medical CollegeAffiliated Hospital of Chengdu UniversityChengdu UniversityChengdu610106China
- Department of Clinical PharmacySchool of PharmacyZunyi Medical UniversityZunyi563006China
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Dizaj SM, Kouhsoltani M, Pourreza K, Sharifi S, Abdolahinia ED. Preparation, Characterization, and Evaluation of the Anticancer Effect of Mesoporous Silica Nanoparticles Containing Rutin and Curcumin. Pharm Nanotechnol 2024; 12:269-275. [PMID: 37594097 DOI: 10.2174/2211738511666230818092706] [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: 05/18/2023] [Revised: 06/25/2023] [Accepted: 07/13/2023] [Indexed: 08/19/2023]
Abstract
AIMS AND OBJECTIVE The aim of this study was the preparation of mesoporous silica nanoparticles co-loaded with rutin and curcumin (Rut-Cur-MSNs) and the assessment of its physicochemical properties as well as its cytotoxicity on the head and neck cancer cells (HN5). Besides, ROS generation of HN5 cells exposed to Rut-Cur-MSNs was evaluated. Several investigations showed that rutin and curcumin have potential effects as anticancer phytochemicals; however, their low aqueous solubility and poor bioavailability limited their applications. The assessment of physicochemical properties and anticancer effect of prepared nanoparticles was the objective of this study. METHODS The physicochemical properties of produced nanoparticles were evaluated. The toxicity of Rut-Cur-MSNs on HN5 cells was assessed. In addition, the ROS production in cells treated with Rut- Cur-MSNs was assessed compared to control untreated cells. RESULTS The results showed that Rut-Cur-MSNs have mesoporous structure, nanometer size and negative surface charge. The X-ray diffraction pattern showed that the prepared nanoparticles belong to the family of silicates named MCM-41. The cytotoxicity of Rut-Cur-MSNs at 24 h was significantly higher than that of rutin-loaded MSNs (Rut-MSNs) and curcumin-loaded MSNs (Cur-MSNs) (p<0.05). CONCLUSION The achieved results recommend that the prepared mesoporous silica nanoparticles containing rutin and curcumin can be a useful nanoformulation for the treatment of cancer. The produced nanomaterial in this study can be helpful for cancer therapy.
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Affiliation(s)
- Solmaz Maleki Dizaj
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Kouhsoltani
- Oral and Maxillofacial Department of Pathology, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kosar Pourreza
- Oral and Maxillofacial Department of Pathology, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology (RCPN), Tabriz University of Medical Sciences, Tabriz, Iran
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Dizaj SM, Rezaei Y, Namaki F, Sharifi S, Abdolahinia ED. Effect of Curcumin-containing Nanofibrous Gelatin-hydroxyapatite Scaffold on Proliferation and Early Osteogenic Differentiation of Dental Pulp Stem Cells. Pharm Nanotechnol 2024; 12:262-268. [PMID: 37592779 DOI: 10.2174/2211738511666230817102159] [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: 02/20/2023] [Revised: 06/11/2023] [Accepted: 07/13/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND In recent years, the electrospinning method has received attention because of its usage in producing a mimetic nanocomposite scaffold for tissue regeneration. Hydroxyapatite and gelatin are suitable materials for producing scaffolds, and curcumin has the osteogenesis induction effect. AIMS This study aimed to evaluate the toxicity and early osteogenic differentiation stimulation of nanofibrous gelatin-hydroxyapatite scaffold containing curcumin on dental pulp stem cells (DPSCs). OBJECTIVE The objective of the present investigation was the evaluation of the proliferative effect and primary osteogenic stimulation of DPSCs with a nanofibrous gelatin-hydroxyapatite scaffold containing curcumin. Hydroxyapatite and gelatin were used as suitable and biocompatible materials to make a scaffold suitable for stimulating osteogenesis. Curcumin was added to the scaffold as an osteogenic differentiation- enhancing agent. METHODS The effect of nano-scaffold on the proliferation of DPSCs was evaluated. The activity of alkaline phosphatase (ALP) as the early osteogenic marker was considered to assess primary osteogenesis stimulation in DPSCs. RESULTS The nanofibrous gelatin-hydroxyapatite scaffold containing curcumin significantly increased the proliferation and the ALP activity of DPSCs (P<0.05). The proliferative effect was insignificant in the first 2 days, but the scaffold increased cell proliferation by more than 40% in the fourth and sixth days. The prepared scaffold increased the activity of the ALP of DPSCs by 60% compared with the control after 14 days (p<0.05). CONCLUSION The produced nanofibrous gelatin-hydroxyapatite scaffold containing curcumin can be utilized as a potential candidate in tissue engineering and regeneration of bone and tooth. FUTURE PROSPECTS The prepared scaffold in the present study could be a beneficial biomaterial for tissue engineering and the regeneration of bone and tooth soon.
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Affiliation(s)
- Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yashar Rezaei
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Namaki
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
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Lestari U, Muhaimin M, Chaerunisaa AY, Sujarwo W. Improved Solubility and Activity of Natural Product in Nanohydrogel. Pharmaceuticals (Basel) 2023; 16:1701. [PMID: 38139827 PMCID: PMC10747279 DOI: 10.3390/ph16121701] [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: 09/26/2023] [Revised: 10/19/2023] [Accepted: 10/22/2023] [Indexed: 12/24/2023] Open
Abstract
With the development of technology, natural material components are widely used in various fields of science. Natural product components in phytochemical compounds are secondary metabolites produced by plants; they have been shown to have many pharmacological activities. Phytochemical compounds obtained from plants have an important role in herbal medicine. Herbal medicine is safer and cheaper than synthetic medicine. However, herbal medicines have weaknesses, such as low solubility, less stability, low bioavailability, and experiencing physical and chemical degradation, reducing their pharmacological activity. Recent herbal nano-delivery developments are mostly plant-based. A nanotechnology-based system was developed to deliver herbal therapies with better bioavailability, namely the nanohydrogel system. Nanohydrogel is a delivery system that can overcome the disadvantages of using herbal compounds because it can increase solubility, increase pharmacological activity and bioavailability, reduce toxicity, slow delivery, increase stability, improve biodistribution, and prevent physical or chemical degradation. This review article aimed to provide an overview of recent advances in developing nanohydrogel formulations derived from natural ingredients to increase solubility and pharmacological activity, as well as a summary of the challenges faced by delivery systems based on nanohydrogel derived from natural materials. A total of 25 phytochemicals derived from natural products that have been developed into nanohydrogel were proven to increase the activity and solubility of these chemical compounds.
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Affiliation(s)
- Uce Lestari
- Doctoral Program, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
- Department of Pharmacy, Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi 36361, Indonesia
| | - Muhaimin Muhaimin
- Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
- Center of Herbal Study, Universitas Padjadjaran, Sumedang 45363, Indonesia
| | - Anis Yohana Chaerunisaa
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
| | - Wawan Sujarwo
- Ethnobotany Research Group, Research Center for Ecology and Ethnobiology, National Research and Innovation Agency (BRIN), Cibinong, Bogor 16911, Indonesia
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Saharkhiz S, Zarepour A, Zarrabi A. Empowering Cancer Therapy: Comparing PEGylated and Non-PEGylated Niosomes Loaded with Curcumin and Doxorubicin on MCF-7 Cell Line. Bioengineering (Basel) 2023; 10:1159. [PMID: 37892889 PMCID: PMC10604767 DOI: 10.3390/bioengineering10101159] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 09/03/2023] [Accepted: 09/29/2023] [Indexed: 10/29/2023] Open
Abstract
Cancer remains an enduring challenge in modern society, prompting relentless pursuits to confront its complexities. However, resistance often emerges against conventional treatments, driven by their inherent limitations such as adverse effects and limited solubility. Herein, we spotlight a remarkable solution; a niosomal platform engineered to tandemly ferry two potent agents, doxorubicin (DOX) and curcumin (CUR). Notably, we delve into the pivotal role of PEGylation, unraveling its impact on therapeutic efficacy. These niosomes consist of Span 60, Tween 60, and cholesterol with a molar ratio of 5:2:3, which were prepared via a thin film hydration method. The physicochemical characterization of particles was performed using DLS, zeta potential measurement, SEM, and FTIR analysis. In addition, their encapsulation efficiency and release profile were determined using the HPLC method. Finally, their cytotoxicity and biocompatibility effects were checked by performing an MTT assay test on the MCF7 and L929 cell lines. The obtained results confirmed the successful fabrication of co-loaded niosomal structures with and without PEG coating. The fabricated nanoparticles had sizes in the range of 100 to 200 nm with a surface charge of about -18 mV for particles without PEG coating and -40 mV for coated particles. Notably, DOX encapsulation efficiency leaps from 20% to 62% in the transition from uncoated to coated, while CUR exhibits an impressive surge from 80% to 95%. The drug release was more controlled and slower in the coated sample. Finally, the MTT results confirmed the biocompatibility and synergistic effect of the simultaneous use of two drugs on cancer cells in the PEGylated niosomal particle. Based on the results, PEGylated niosomal particles can be considered adept vehicles for the simultaneous delivery of different chemotherapy cargoes with synergic interaction to overcome cancer.
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Affiliation(s)
- Shaghayegh Saharkhiz
- Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 81746-73441, Iran
| | - Atefeh Zarepour
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Türkiye
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Türkiye
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Zhao C, Zhou X, Cao Z, Ye L, Cao Y, Pan J. Curcumin and analogues against head and neck cancer: From drug delivery to molecular mechanisms. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 119:154986. [PMID: 37506572 DOI: 10.1016/j.phymed.2023.154986] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/05/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023]
Abstract
BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is one of the most life-threatening diseases which also causes economic burden worldwide. To overcome the limitations of traditional therapies, investigation into alternative adjuvant treatments is crucial. PURPOSE Curcumin, a turmeric-derived compound, demonstrates significant therapeutic potential in diverse diseases, including cancer. Furthermore, research focuses on curcumin analogues and novel drug delivery systems, offering approaches for improved efficacy. This review aims to provide a comprehensive overview of curcumin's current findings, emphasizing its mechanisms of anti-HNSCC effects and potential for clinical application. METHOD An electronic search of Web of Science, MEDLINE, and Embase was conducted to identify literature about the application of curcumin or analogues in HNSCC. Titles and abstracts were screened to identify potentially eligible studies. Full-text articles will be obtained and independently evaluated by two authors to make the decision of inclusion in the review. RESULTS Curcumin's clinical application is hindered by poor bioavailability, prompting the exploration of methods to enhance it, such as curcumin analogues and novel drug delivery systems. Curcumin could exhibit anti-cancer effects by targeting cancer cells and modulating the tumor microenvironment in HNSCC. Mechanisms of action include cell cycle arrest, apoptosis promotion, reactive oxygen species induction, endoplasmic reticulum stress, inhibition of epithelial-mesenchymal transition, attenuation of extracellular matrix degradation, and modulation of tumor metabolism in HNSCC cells. Curcumin also targets various components of the tumor microenvironment, including cancer-associated fibroblasts, innate and adaptive immunity, and lymphovascular niches. Furthermore, curcumin enhances the anti-cancer effects of other drugs as adjunctive therapy. Two clinical trials report its potential clinical applications in treating HNSCC. CONCLUSION Curcumin has demonstrated therapeutic potential in HNSCC through in vitro and in vivo studies. Its effectiveness is attributed to its ability to modulate cancer cells and interact with the intricate tumor microenvironment. The development of curcumin analogues and novel drug delivery systems has shown promise in improving its bioavailability, thereby expanding its clinical applications. Further research and exploration in this area hold great potential for harnessing the full therapeutic benefits of curcumin in HNSCC treatment.
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Affiliation(s)
- Chengzhi Zhao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 1 Section 3rd, Renmin Nan Road, Chengdu 610041, PR China
| | - Xueer Zhou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 1 Section 3rd, Renmin Nan Road, Chengdu 610041, PR China
| | - Zhiwei Cao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 1 Section 3rd, Renmin Nan Road, Chengdu 610041, PR China
| | - Li Ye
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 1 Section 3rd, Renmin Nan Road, Chengdu 610041, PR China
| | - Yubin Cao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 1 Section 3rd, Renmin Nan Road, Chengdu 610041, PR China.
| | - Jian Pan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No. 1 Section 3rd, Renmin Nan Road, Chengdu 610041, PR China.
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Xi G, Dong Q, Yang B, Jiao D, Khan S. Curcumin's Dose-Dependent Attenuation of Gastric Cancer Cell Progression Via the PI3K Pathway Blockade. Dose Response 2023; 21:15593258231203585. [PMID: 37933268 PMCID: PMC10625731 DOI: 10.1177/15593258231203585] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2023] Open
Abstract
Background: Gastric cancer stands as a primary cause of cancer-related deaths worldwide, making the discovery of new therapeutic agents essential for enhancing treatment outcomes. Curcumin, a polyphenolic compound found in turmeric (Curcuma longa), has demonstrated potential in multiple cancer types due to its anti-cancer characteristics. This research aimed to examine the impact of curcumin on gastric cancer cell growth, migration, and invasion, as well as its influence on the phosphoinositide 3-kinase (PI3K) signaling cascade. Methods: Gastric cancer cell lines were exposed to varying curcumin concentrations, followed by assessments of cell viability, migration, and invasion. Furthermore, gene and protein expression levels associated with the PI3K signaling cascade were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results: The findings revealed a dose-dependent decrease in cell viability, migration, and invasion in gastric cancer cells treated with curcumin. Additionally, curcumin administration led to the downregulation of key genes and proteins within the PI3K signaling process, such as PI3K, Akt, and mTOR. Conclusion: These findings propose that curcumin may exercise its anti-cancer effects on gastric cancer cells, partly by suppressing the PI3K signaling pathway. This study's outcomes support curcumin's potential as a therapeutic agent for gastric cancer and encourage further exploration of its underlying molecular mechanisms and in vivo effectiveness.
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Affiliation(s)
- Gen Xi
- Department of General Surgery, Baoji People’s Hospital, Baoji, China
| | - Qingtao Dong
- Department of General Surgery, Baoji People’s Hospital, Baoji, China
| | - Bo Yang
- Department of General Surgery, Baoji People’s Hospital, Baoji, China
| | - Desheng Jiao
- Department of General Surgery, Xi'an Labor Union Hospital, Xi'an, China
| | - Shahanavaj Khan
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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22
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Huang B, Yin Z, Zhou F, Su J. Functional anti-bone tumor biomaterial scaffold: construction and application. J Mater Chem B 2023; 11:8565-8585. [PMID: 37415547 DOI: 10.1039/d3tb00925d] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2023]
Abstract
Bone tumors, including primary bone tumors and bone metastases, have been plagued by poor prognosis for decades. Although most tumor tissue is removed, clinicians are still confronted with the dilemma of eliminating residual cancer cells and regenerating defective bone tissue after surgery. Therefore, functional biomaterial scaffolds are considered to be the ideal candidates to bridge defective tissues and restrain cancer recurrence. Through functionalized structural modifications or coupled therapeutic agents, they provide sufficient mechanical strength and osteoinductive effects while eliminating cancer cells. Numerous novel approaches such as photodynamic, photothermal, drug-conjugated, and immune adjuvant-assisted therapies have exhibited remarkable efficacy against tumors while exhibiting low immunogenicity. This review summarizes the progress of research on biomaterial scaffolds based on different functionalization strategies in bone tumors. We also discuss the feasibility and advantages of the combined application of multiple functionalization strategies. Finally, potential obstacles to the clinical translation of anti-tumor bone bioscaffolds are highlighted. This review will provide valuable references for future advanced biomaterial scaffold design and clinical bone tumor therapy.
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Affiliation(s)
- Biaotong Huang
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- Wenzhou Institute of Shanghai University, Wenzhou 325000, China
| | - Zhifeng Yin
- Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200444, China
| | - Fengjin Zhou
- Department of Orthopedics, Honghui Hospital, Xi'an Jiao Tong University, Xi'an, 710000, China.
| | - Jiacan Su
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
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Hussain A, Kumar A, Uttam V, Sharma U, Sak K, Saini RV, Saini AK, Haque S, Tuli HS, Jain A, Sethi G. Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances. ENVIRONMENTAL RESEARCH 2023; 233:116476. [PMID: 37348632 DOI: 10.1016/j.envres.2023.116476] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 06/05/2023] [Accepted: 06/19/2023] [Indexed: 06/24/2023]
Abstract
Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.
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Affiliation(s)
- Arif Hussain
- School of Life Sciences, Manipal Academy of Higher Education, 345050, Dubai, United Arab Emirates
| | - Ajay Kumar
- University Center for Research & Development (UCRD), Chandigarh University, Mohali, 140413, Punjab, India; Biotechnology Engineering and Food Technology, Chandigarh University, Mohali, 140413, Punjab, India
| | - Vivek Uttam
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Bathinda, Punjab, India
| | - Uttam Sharma
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Bathinda, Punjab, India
| | | | - Reena V Saini
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, 133207, India
| | - Adesh K Saini
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, 133207, India; Faculty of Agriculture, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, 133207, India
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, 45142, Saudi Arabia; Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon; Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Hardeep Singh Tuli
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, 133207, India
| | - Aklank Jain
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Bathinda, Punjab, India.
| | - Gautam Sethi
- Department of Pharmacology and NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
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Mundekkad D, Cho WC. Applications of Curcumin and Its Nanoforms in the Treatment of Cancer. Pharmaceutics 2023; 15:2223. [PMID: 37765192 PMCID: PMC10536212 DOI: 10.3390/pharmaceutics15092223] [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: 07/03/2023] [Revised: 08/04/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
Due to the diverse medicinal and pharmacokinetic properties of turmeric, it is well-known in the therapeutic, pharmaceutic, nutraceutical, cosmetic, and dietary industries. It gained importance due to its multitude of properties, such as wound-healing, anti-inflammatory, anti-oxidant, anti-microbial, cytoprotective, anti-aging, anti-cancer, and immunomodulatory effects. Even though the natural healing effect of turmeric has been known to Indians as early as 2500 BCE, the global demand for turmeric has increased only recently. A major reason for the beneficiary activities of turmeric is the presence of the yellow-colored polyphenolic compound called curcumin. Many studies have been carried out on the various properties of curcumin and its derivatives. Despite its low bioavailability, curcumin has been effectively used for the treatment of many diseases, such as cardiovascular and neurological diseases, diabetes, arthritis, and cancer. The advent of nanobiotechnology has further opened wide opportunities to explore and expand the use of curcumin in the medical field. Nanoformulations using curcumin and its derivatives helped to design new treatment modalities, specifically in cancer, because of the better bioavailability and solubility of nanocurcumin when compared to natural curcumin. This review deals with the various applications of curcumin nanoparticles in cancer therapy and broadly tries to understand how it affect the immunological status of the cancer cell.
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Affiliation(s)
- Deepa Mundekkad
- Department of Biotechnology, Nehru Arts and Science College, Thirumalayampalayam, Coimbatore 641105, India
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
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Wu X, Yang Y. Research progress on drug delivery systems for curcumin in the treatment of gastrointestinal tumors. World J Gastrointest Oncol 2023; 15:1342-1348. [PMID: 37663948 PMCID: PMC10473931 DOI: 10.4251/wjgo.v15.i8.1342] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/11/2023] [Accepted: 07/11/2023] [Indexed: 08/10/2023] Open
Abstract
Curcumin is a natural compound with a diketone structure, which can control the growth, metastasis, recurrence, neovascularization, invasion, and drug resistance of gastrointestinal tumors by inhibiting nuclear factor κB, overexpression of tumor cells, vascular endothelial growth factor, etc. However, due to the low bioavailability of curcumin formulation, it did not fully exert its pharmacological effects, and its application and development in the treatment of various malignant tumors are still limited. This review summarizes the research on drug delivery systems of curcumin combating digestive tract tumors in order to further reduce the toxic side effects of curcumin-containing drugs and fully exert their pharmacological activities, and improve their bioavailability and clinical value.
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Affiliation(s)
- Xin Wu
- Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
| | - Yang Yang
- Department of Respiratory Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
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26
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Cacciola NA, Cuciniello R, Petillo GD, Piccioni M, Filosa S, Crispi S. An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments. Int J Mol Sci 2023; 24:12587. [PMID: 37628772 PMCID: PMC10454892 DOI: 10.3390/ijms241612587] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/01/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Due to the progressive ageing of the human population, the number of cancer cases is increasing. For this reason, there is an urgent need for new treatments that can prolong the lives of cancer patients or ensure them a good quality of life. Although significant progress has been made in the treatment of cancer in recent years and the survival rate of patients is increasing, limitations in the use of conventional therapies include the frequent occurrence of side effects and the development of resistance to chemotherapeutic agents. These limitations are prompting researchers to investigate whether combining natural agents with conventional drugs could have a positive therapeutic effect in cancer treatment. Several natural bioactive compounds, especially polyphenols, have been shown to be effective against cancer progression and do not exert toxic effects on healthy tissues. Many studies have investigated the possibility of combining polyphenols with conventional drugs as a novel anticancer strategy. Indeed, this combination often has synergistic benefits that increase drug efficacy and reduce adverse side effects. In this review, we provide an overview of the studies describing the synergistic effects of curcumin, a polyphenol that has been shown to have extensive cytotoxic functions against cancer cells, including combined treatment. In particular, we have described the results of recent preclinical and clinical studies exploring the pleiotropic effects of curcumin in combination with standard drugs and the potential to consider it as a promising new tool for cancer therapy.
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Affiliation(s)
- Nunzio Antonio Cacciola
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy;
- Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
| | - Rossana Cuciniello
- Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino, 111, 80131 Naples, Italy; (R.C.); (M.P.)
- IRCCS Neuromed, 86077 Isernia, Italy
| | | | - Miriam Piccioni
- Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino, 111, 80131 Naples, Italy; (R.C.); (M.P.)
| | - Stefania Filosa
- Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino, 111, 80131 Naples, Italy; (R.C.); (M.P.)
- IRCCS Neuromed, 86077 Isernia, Italy
| | - Stefania Crispi
- Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino, 111, 80131 Naples, Italy; (R.C.); (M.P.)
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Huang M, Zhai BT, Fan Y, Sun J, Shi YJ, Zhang XF, Zou JB, Wang JW, Guo DY. Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy. Int J Nanomedicine 2023; 18:4275-4311. [PMID: 37534056 PMCID: PMC10392909 DOI: 10.2147/ijn.s410688] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 06/19/2023] [Indexed: 08/04/2023] Open
Abstract
Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.
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Affiliation(s)
- Mian Huang
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Bing-Tao Zhai
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Yu Fan
- School of Basic Medicine, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Jing Sun
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Ya-Jun Shi
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Xiao-Fei Zhang
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Jun-Bo Zou
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Jia-Wen Wang
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
| | - Dong-Yan Guo
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
- Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China
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Vieira IRS, Tessaro L, Lima AKO, Velloso IPS, Conte-Junior CA. Recent Progress in Nanotechnology Improving the Therapeutic Potential of Polyphenols for Cancer. Nutrients 2023; 15:3136. [PMID: 37513554 PMCID: PMC10384266 DOI: 10.3390/nu15143136] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 07/06/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
Polyphenols derived from fruits, vegetables, and plants are bioactive compounds potentially beneficial to human health. Notably, compounds such as quercetin, curcumin, epigallocatechin-3-gallate (EGCG), and resveratrol have been highlighted as antiproliferative agents for cancer. Due to their low solubility and limited bioavailability, some alternative nanotechnologies have been applied to encapsulate these compounds, aiming to improve their efficacy against cancer. In this comprehensive review, we evaluate the main nanotechnology approaches to improve the therapeutic potential of polyphenols against cancer using in vitro studies and in vivo preclinical models, highlighting recent advancements in the field. It was found that polymeric nanomaterials, lipid-based nanomaterials, inorganic nanomaterials, and carbon-based nanomaterials are the most used classes of nanocarriers for encapsulating polyphenols. These delivery systems exhibit enhanced antitumor activity and pro-apoptotic effects, particularly against breast, lung, prostate, cervical, and colorectal cancer cells, surpassing the performance of free bioactive compounds. Preclinical trials in xenograft animal models have revealed decreased tumor growth after treatment with polyphenol-loaded delivery systems. Moreover, the interaction of polyphenol co-delivery systems and polyphenol-drug delivery systems is a promising approach to increase anticancer activity and decrease chemotherapy side effects. These innovative approaches hold significant implications for the advancement of clinical cancer research.
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Affiliation(s)
- Italo Rennan Sousa Vieira
- Analytical and Molecular Laboratorial Center (CLAn), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-598, RJ, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Bio-Chemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Graduate Program in Food Science (PPGCAL), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
| | - Leticia Tessaro
- Analytical and Molecular Laboratorial Center (CLAn), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-598, RJ, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Bio-Chemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
| | - Alan Kelbis Oliveira Lima
- Nanobiotechnology Laboratory, Institute of Biology (IB), Department of Genetics and Morphology, University of Brasilia, Brasilia 70910-900, DF, Brazil
| | - Isabela Portella Silva Velloso
- Analytical and Molecular Laboratorial Center (CLAn), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-598, RJ, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Bio-Chemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
| | - Carlos Adam Conte-Junior
- Analytical and Molecular Laboratorial Center (CLAn), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-598, RJ, Brazil
- Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Bio-Chemistry, Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
- Graduate Program in Food Science (PPGCAL), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro 21941-909, RJ, Brazil
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Laneri F, Conte C, Parisi C, Catanzano O, Fraix A, Quaglia F, Sortino S. On the photobehaviour of curcumin in biocompatible hosts: The role of H-abstraction in the photodegradation and photosensitization. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2023; 245:112756. [PMID: 37454510 DOI: 10.1016/j.jphotobiol.2023.112756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 06/24/2023] [Accepted: 07/10/2023] [Indexed: 07/18/2023]
Abstract
Curcumin (CUR) is a naturally occurring pigment extensively studied due to its therapeutic activity and delivered by suitable nanocarriers to overcome poor solubility in aqueous media. The significant absorption of CUR in the visible blue region has prompted its use as a potential phototherapeutic agent in treating infectious and cancer diseases, although the mechanism underlying the phototoxic effects is still not fully understood. This contribution investigates the photobehaviour of CUR within polymeric micelles, microemulsions, and zein nanoparticles, chosen as biocompatible nanocarriers, and human serum albumin as a representative biomolecule. Spectroscopic studies indicate that in all host systems, the enolic tautomeric form of CUR is converted in a significant amount of the diketo form because of the perturbation of the intramolecular hydrogen bond. This leads to intermolecular H-abstraction from the host components by the lowest excited triplet state of CUR with the formation of the corresponding ketyl radical, detected by nanosecond laser flash photolysis. This radical is oxidized by molecular oxygen, likely generating peroxyl and hydroperoxyl radical species, unless in Zein, reasonably due to the poor availability of oxygen in the closely packed structure of this nanocarrier. In contrast, no detectable formation of singlet oxygen was revealed in all the systems. Overall these results highlight the key role of the H-abstraction process over singlet oxygen sensitization as a primary photochemical pathway strictly dictated by the specific features of the microenvironment, providing new insights into the photoreactivity of CUR in biocompatible hosts that can also be useful for a better understanding of its phototoxicity mechanism.
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Affiliation(s)
- Francesca Laneri
- PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125 Catania, Italy
| | - Claudia Conte
- Drug Delivery Laboratory, Department of Pharmacy, University of Napoli Federico II, I-80131 Napoli, Italy
| | - Cristina Parisi
- PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125 Catania, Italy
| | - Ovidio Catanzano
- Drug Delivery Laboratory, Department of Pharmacy, University of Napoli Federico II, I-80131 Napoli, Italy
| | - Aurore Fraix
- PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125 Catania, Italy.
| | - Fabiana Quaglia
- Drug Delivery Laboratory, Department of Pharmacy, University of Napoli Federico II, I-80131 Napoli, Italy
| | - Salvatore Sortino
- PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125 Catania, Italy
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Silvestre F, Santos C, Silva V, Ombredane A, Pinheiro W, Andrade L, Garcia M, Pacheco T, Joanitti G, Luz G, Carneiro M. Pharmacokinetics of Curcumin Delivered by Nanoparticles and the Relationship with Antitumor Efficacy: A Systematic Review. Pharmaceuticals (Basel) 2023; 16:943. [PMID: 37513855 PMCID: PMC10384157 DOI: 10.3390/ph16070943] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 04/06/2023] [Accepted: 04/24/2023] [Indexed: 07/30/2023] Open
Abstract
Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor. Although it is a pleiotropic molecule, curcumin's free form, which is lipophilic, has low bioavailability and is rapidly metabolized, limiting its clinical use. With the advances in techniques for loading curcumin into nanostructures, it is possible to improve its bioavailability and extend its applications. In this review, we gather evidence about the comparison of the pharmacokinetics (biodistribution and bioavailability) between free curcumin (Cur) and nanostructured curcumin (Cur-NPs) and their respective relationships with antitumor efficacy. The search was performed in the following databases: Cochrane, LILACS, Embase, MEDLINE/Pubmed, Clinical Trials, BSV regional portal, ScienceDirect, Scopus, and Web of Science. The selected studies were based on studies that used High-Performance Liquid Chromatography (HPLC) as the pharmacokinetics evaluation method. Of the 345 studies initially pooled, 11 met the inclusion criteria and all included studies classified as high quality. In this search, a variety of nanoparticles used to deliver curcumin (polymeric, copolymeric, nanocrystals, nanovesicles, and nanosuspension) were found. Most Cur-NPs presented negative Zeta potential ranging from -25 mV to 12.7 mV, polydispersion index (PDI) ranging from 0.06 to 0.283, and hydrodynamic diameter ranging from 30.47 to 550.1 nm. Selected studies adopted mainly oral and intravenous administrations. In the pharmacokinetics analysis, samples of plasma, liver, tumor, lung, brain, kidney, and spleen were evaluated. The administration of curcumin, in nanoparticle systems, resulted in a higher level of curcumin in tumors compared to free curcumin, leading to an improved antitumor effect. Thus, the use of nanoparticles can be a promising alternative for curcumin delivery since this improves its bioavailability.
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Affiliation(s)
- Fernanda Silvestre
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
| | - Carolina Santos
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Biomedical Engineering (PPGEB), Faculty of Gama, University of Brasilia, Special Area of Industry Projection A, Brasilia 72444-240, Brazil
| | - Vitória Silva
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
| | - Alicia Ombredane
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Department of Nutrition, Faculty of Health Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
| | - Willie Pinheiro
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Sciences and Technologies in Health, Faculty of Ceilândia, Campus Darcy Ribeiro, University of Brasilia, Brasilia 72220-275, Brazil
| | - Laise Andrade
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
| | - Mônica Garcia
- Post-Graduate Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
| | - Thyago Pacheco
- Post-Graduate Program in Animal Biology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
| | - Graziella Joanitti
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Sciences and Technologies in Health, Faculty of Ceilândia, Campus Darcy Ribeiro, University of Brasilia, Brasilia 72220-275, Brazil
| | - Glécia Luz
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Biomedical Engineering (PPGEB), Faculty of Gama, University of Brasilia, Special Area of Industry Projection A, Brasilia 72444-240, Brazil
| | - Marcella Carneiro
- Laboratory of Bioactive Compounds and Nanobiotechnology (LCBNano), Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Nanoscience and Nanobiotechnology, Institute of Biological Sciences, Campus Darcy Ribeiro, University of Brasilia, Brasilia 70910-900, Brazil
- Post-Graduate Program in Biomedical Engineering (PPGEB), Faculty of Gama, University of Brasilia, Special Area of Industry Projection A, Brasilia 72444-240, Brazil
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Wang S, He W, Li W, Zhou JR, Du Z. Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation. Molecules 2023; 28:4900. [PMID: 37446563 DOI: 10.3390/molecules28134900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/13/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. METHOD To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. RESULTS Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. CONCLUSION The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.
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Affiliation(s)
- Shanshan Wang
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 511400, China
| | - Wenjiang He
- R&D Centre, Infinitus (China) Company Ltd., Guangzhou 510520, China
| | - Wenzhi Li
- R&D Centre, Infinitus (China) Company Ltd., Guangzhou 510520, China
| | - Jin-Rong Zhou
- Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Zhiyun Du
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 511400, China
- Conney Allan Biotechnology Company Ltd., Guangzhou 510095, China
- Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 511400, China
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Pouliquen DL, Trošelj KG, Anto RJ. Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future. Pharmaceutics 2023; 15:1612. [PMID: 37376060 DOI: 10.3390/pharmaceutics15061612] [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: 04/28/2023] [Revised: 05/21/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they have produced on a multitude of pathways involved in carcinogenesis and tumor progression have been provided. As this wealth of data was obtained in settings of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules that can be combined with several anticancer drugs to reverse the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put among the prospects for the future research related to the importance of these molecules in cancer research.
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Affiliation(s)
- Daniel L Pouliquen
- Université d'Angers, Inserm, CNRS, Nantes Université, CRCI2NA, F-49000 Angers, France
| | - Koraljka Gall Trošelj
- Laboratory for Epigenomics, Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia
| | - Ruby John Anto
- Molecular Bioassay Laboratory, Institute of Advanced Virology, Thiruvananthapuram 695317, India
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Soleymanijadidi P, Moradi M, Hamedirad F, Ghanavati Z, Maleki Dizaj S, Salatin S. Nanocurcumin Release from Self-Cured Acrylic Resins; Effects on Antimicrobial Action and Flexural Strength. Bioengineering (Basel) 2023; 10:bioengineering10050559. [PMID: 37237629 DOI: 10.3390/bioengineering10050559] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/29/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The placement of orthodontic appliances into the oral area can lead to infection, inflammatory and gingival collapse. Using an antimicrobial and anti-inflammatory material in the matrix of orthodontic appliance may help to reduce these issues. This study aimed to assess the release pattern, the antimicrobial action and the flexural strength of self-cured acrylic resins after adding different weight percentages of curcumin nanoparticles (nanocurcumin). In this in-vitro study, 60 acrylic resin samples were divided into five groups (n = 12) based on the weight percentage of curcumin nanoparticles added to the acrylic powder (0 for control, 0.5, 1, 2.5, and 5%). Then, the dissolution apparatus was used for the release assessment of nanocurcumin form the resins. For antimicrobial action assessment, the disk diffusion method was used and a three-point bending test was performed with a speed of 5 mm/min to determine the flexural strength. Data were analyzed using one-way analysis of variance (ANOVA) and Post-Hoc Tukey tests (with p < 0.05 as significant level). The microscopic images showed the homogeny distribution of nanocuricumin in self-cured acrylic resins in varied concentrations. The release pattern showed a two-step release pattern for all concentrations of nanocurcumin. The one-way ANOVA outcomes indicated that adding curcumin nanoparticles to self-cured resin increased the diameter of the inhibition zones for the groups against Streptococcus mutans (S. mutans) significantly (p < 0.0001). Additionally, as the weight percentage of curcumin nanoparticles increased, the flexural strength decreased (p < 0.0001). However, all strength values were higher than the standard value (50 MPa). No significant difference was detected between the control group and the group with 0.5 percent (p = 0.57). Considering the proper release pattern and the potent antimicrobial activity of curcumin nanoparticles, then the preparing self-cured resins containing curcumin nanoparticles can be beneficial for antimicrobial aims without damaging the flexural strength to use in orthodontic removable applications.
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Affiliation(s)
- Parsa Soleymanijadidi
- Dental Materials Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-4774, Iran
| | - Meysam Moradi
- Dental Materials Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-4774, Iran
| | - Fahimeh Hamedirad
- Dental Materials Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-4774, Iran
| | - Zahra Ghanavati
- Dental Materials Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-4774, Iran
| | - Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz 51548-53431, Iran
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz 51548-53431, Iran
| | - Sara Salatin
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz 51548-53431, Iran
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Nawaz A, Latif MS, Shah MKA, Elsayed TM, Ahmad S, Khan HA. Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery. Gels 2023; 9:gels9030201. [PMID: 36975650 PMCID: PMC10048031 DOI: 10.3390/gels9030201] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 02/28/2023] [Accepted: 03/03/2023] [Indexed: 03/09/2023] Open
Abstract
Curcumin, a natural phenolic compound, exhibits poor absorption and extensive first pass metabolism after oral administration. In the present study, curcumin-chitosan nanoparticles (cur-cs-np) were prepared and incorporated into ethyl cellulose patches for the management of inflammation via skin delivery. Ionic gelation method was used for the preparation of nanoparticles. The prepared nanoparticles were evaluated for size, zetapotential, surface morphology, drug content, and % encapsulation efficiency. The nanoparticles were then incorporated into ethyl cellulose-based patches using solvent evaporation technique. ATR-FTIR was used to study/assess incompatibility between drug and excipients. The prepared patches were evaluated physiochemically. The in vitro release, ex vivo permeation, and skin drug retention studies were carried out using Franz diffusion cells and rat skin as permeable membrane. The prepared nanoparticles were spherical, with particle size in the range of 203–229 nm, zetapotential 25–36 mV, and PDI 0.27–0.29 Mw/Mn. The drug content and %EE were 53% and 59%. Nanoparticles incorporated patches are smooth, flexible, and homogenous. The in vitro release and ex vivo permeation of curcumin from nanoparticles were higher than the patches, whereas the skin retention of curcumin was significantly higher in case of patches. The developed patches deliver cur-cs-np into the skin, where nanoparticles interact with skin negative charges and hence result in higher and prolonged retention in the skin. The higher concentration of drug in the skin helps in better management of inflammation. This was shown by anti-inflammatory activity. The inflammation (volume of paw) was significantly reduced when using patches as compared to nanoparticles. It was concluded that the incorporation of cur-cs-np into ethyl cellulose-based patches results in controlled release and hence enhanced anti-inflammatory activity.
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Affiliation(s)
- Asif Nawaz
- Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan
- Correspondence:
| | - Muhammad Shahid Latif
- Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan
| | - Muhammad Khurshid Alam Shah
- Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan
| | - Tarek M. Elsayed
- Pharmaceutical Technology Department, Faculty of Pharmacy, Sultan Zainal Abidin University, Besut Kampus, Besut 22200, Malaysia
| | - Saeed Ahmad
- Institute of Biotechnology and Microbiology, Bacha Khan University, Charsadda 24420, Pakistan
| | - Hamid Ali Khan
- Directorate of ORIC, Bacha Khan University, Charsadda 24420, Pakistan
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Su SC, Hsin CH, Lu YT, Chuang CY, Ho YT, Yeh FL, Yang SF, Lin CW. EF-24, a Curcumin Analog, Inhibits Cancer Cell Invasion in Human Nasopharyngeal Carcinoma through Transcriptional Suppression of Matrix Metalloproteinase-9 Gene Expression. Cancers (Basel) 2023; 15:1552. [PMID: 36900342 PMCID: PMC10000445 DOI: 10.3390/cancers15051552] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/17/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
Cancer metastasis is a main cause of failure in treating subjects with nasopharyngeal carcinoma (NPC) and is frequently linked to high death rates. EF-24, an analog of curcumin, has exhibited many anti-cancer properties and enhanced bioavailability over curcumin. Nevertheless, the effects of EF-24 on the invasiveness of NPC are poorly understood. In this study, we demonstrated that EF-24 effectively inhibited TPA-induced motility and invasion responses of human NPC cells but elicited very limited cytotoxicity. In addition, the TPA-induced activity and expression of matrix metalloproteinase-9 (MMP-9), a crucial mediator of cancer dissemination, were found to be reduced in EF-24-treated cells. Our reporter assays revealed that such a reduction in MMP-9 expression by EF-24 was transcriptionally mediated by NF-κB via impeding its nuclear translocation. Further chromatin immunoprecipitation assays displayed that the EF-24 treatment decreased the TPA-induced interaction of NF-κB with the MMP-9 promoter in NPC cells. Moreover, EF-24 inhibited the activation of JNK in TPA-treated NPC cells, and the treatment of EF-24 together with a JNK inhibitor showed a synergistic effect on suppressing TPA-induced invasion responses and MMP-9 activities in NPC cells. Taken together, our data demonstrated that EF-24 restrained the invasiveness of NPC cells through the transcriptional suppression of MMP-9 gene expression, implicating the usefulness of curcumin or its analogs in controlling the spread of NPC.
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Affiliation(s)
- Shih-Chi Su
- Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou 333, Taiwan
| | - Chung-Han Hsin
- Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Yen-Ting Lu
- Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Chun-Yi Chuang
- Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Yu-Ting Ho
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Fang-Ling Yeh
- Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Chiao-Wen Lin
- Institute of Oral Sciences, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung 402, Taiwan
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Ijaz S, Sultana M, Shamim R, Bukhari NI. Development and DoE-ANN based optimization of novel swellable matrix-diffusible doxorubicin loaded zinc oxide nanoflowers using sonochemical-precipitation method. Int J Pharm 2023; 633:122584. [PMID: 36621704 DOI: 10.1016/j.ijpharm.2023.122584] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/27/2022] [Accepted: 01/02/2023] [Indexed: 01/07/2023]
Abstract
This research aimed to acquire doxorubicin loaded zinc oxide nanoflowers (DOX-ZnO-NFs) for intracellular drug cargo possessing a synergistic in-vitro anticancer activity with minimal toxicity. Zinc is the main inorganic metallic component of various enzyme systems and has the possibility of fabrication into the diverse nano-structural forms. An easy absorption and extensive tissue distribution of zinc have made it unique candidate for drug delivery system. Hence, the zinc oxide nanoflowers were prepared with sonochemical-precipitation. The developed system was characterized using the reported methods and was optimized employing design of experiment, coupled with artificial neural network approach. The optimized nanoflowers (DOX-ZnO-NFV) were anionic with particle size of 24 ± 0.05 nm, polydispersity index of <0.5, a zeta potential of -25.68 ± 0.16 mV, yield of 87.40% and encapsulation efficiency of 85.25%. DOX-ZNO-NFV depicted sustained DOX release, around 65.413% release in 30 h at pH 7.4 and assumed Weibull model with its derived parameters, a and b of 22.77 and 0.918, respectively. DOX-ZnO-NFV remained stable on storage for 3 months at 4° C/50% RH and 25° C/60% RH. DOX-ZnO-NFV displayed a zone of inhibition of 13.50 ± 1.25 mm and 25.50 ± 0.98 mm, respectively against gram-positive Staphylococcus aureus and gram-negative Escherichia coli strains, presenting the nanoflowers as self-preservative. DOX-ZnO-NFV exhibited higher in-vitro anticancer activity in Henrietta Lacks cell line, with least hemolysis compared to the free DOX and ZnO-NF. Thus, doxorubicin loaded zinc oxide nanoflowers envisioned to act as better chemotherapeutic cargos with the maximize anticancer activity and minimal toxicity.
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Affiliation(s)
- Sana Ijaz
- Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54000, Pakistan
| | - Misbah Sultana
- Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54000, Pakistan
| | - Rahat Shamim
- Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54000, Pakistan
| | - Nadeem Irfan Bukhari
- Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore 54000, Pakistan.
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Alipour M, Sharifi S, Samiei M, Shahi S, Aghazadeh M, Dizaj SM. Synthesis, characterization, and evaluation of Hesperetin nanocrystals for regenerative dentistry. Sci Rep 2023; 13:2076. [PMID: 36746996 PMCID: PMC9902453 DOI: 10.1038/s41598-023-28267-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 01/16/2023] [Indexed: 02/08/2023] Open
Abstract
Hesperetin (HS), a metabolite of hesperidin, is a polyphenolic component of citrus fruits. This ingredient has a potential role in bone strength and the osteogenic differentiation. The bone loss in the orofacial region may occur due to the inflammation response of host tissues. Nanotechnology applications have been harshly entered the field of regenerative medicine to improve the efficacy of the materials and substances. In the current study, the hesperetin nanocrystals were synthesized and characterized. Then, the anti-inflammatory and antioxidative effects of these nanocrystals were evaluated on inflamed human Dental Pulp Stem Cells (hDPSCs) and monocytes (U937). Moreover, the osteoinduction capacity of these nanocrystals was assessed by gene and protein expression levels of osteogenic specific markers including RUNX2, ALP, OCN, Col1a1, and BSP in hDPSCs. The deposition of calcium nodules in the presence of hesperetin and hesperetin nanocrystals was also assessed. The results revealed the successful fabrication of hesperetin nanocrystals with an average size of 100 nm. The levels of TNF, IL6, and reactive oxygen species (ROS) in inflamed hDPSCs and U937 significantly decreased in the presence of hesperetin nanocrystals. Furthermore, these nanocrystals induced osteogenic differentiation in hDPSCs. These results demonstrated the positive and effective role of fabricated nanocrystal forms of this natural ingredient for regenerative medicine purposes.
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Affiliation(s)
- Mahdieh Alipour
- Dental and Periodontal Research Center, Faculty of Dentistry, Tabriz University of Medical Sciences, Daneshgah St, Golgasht St, Tabriz, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Faculty of Dentistry, Tabriz University of Medical Sciences, Daneshgah St, Golgasht St, Tabriz, Iran
| | - Mohammad Samiei
- Department of Endodontics, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shahriar Shahi
- Dental and Periodontal Research Center, Faculty of Dentistry, Tabriz University of Medical Sciences, Daneshgah St, Golgasht St, Tabriz, Iran
| | - Marziyeh Aghazadeh
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Daneshgah St, Golgasht St, Tabriz, Iran.
| | - Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Faculty of Dentistry, Tabriz University of Medical Sciences, Daneshgah St, Golgasht St, Tabriz, Iran.
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Garshasbi HR, Naghib SM. Smart Stimuli-responsive Alginate Nanogels for Drug Delivery Systems and Cancer Therapy: A Review. Curr Pharm Des 2023; 29:3546-3562. [PMID: 38115614 DOI: 10.2174/0113816128283806231211073031] [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: 09/23/2023] [Revised: 11/13/2023] [Accepted: 11/23/2023] [Indexed: 12/21/2023]
Abstract
Nanogels are three-dimensional networks at the nanoscale level that can be fabricated through physical or chemical processes using polymers. These nanoparticles' biocompatibility, notable stability, efficacious drug-loading capacity, and ligand-binding proficiency make them highly suitable for employment as drug-delivery vehicles. In addition, they exhibit the ability to react to both endogenous and exogenous stimuli, which may include factors such as temperature, illumination, pH levels, and a diverse range of other factors. This facilitates the consistent administration of the drug to the intended site. Alginate biopolymers have been utilized to encapsulate anticancer drugs due to their biocompatible nature, hydrophilic properties, and cost-effectiveness. The efficacy of alginate nano gel-based systems in cancer treatment has been demonstrated through multiple studies that endorse their progress toward clinical implementation. This paper comprehensively reviews alginate and its associated systems in drug delivery systems.
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Affiliation(s)
- Hamid Reza Garshasbi
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology (IUST), Tehran 1684613114, Iran
| | - Seyed Morteza Naghib
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology (IUST), Tehran 1684613114, Iran
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Curcumin: An epigenetic regulator and its application in cancer. Biomed Pharmacother 2022; 156:113956. [DOI: 10.1016/j.biopha.2022.113956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 10/31/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
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Tian Q, Guo Y, Li D, Dong L. Hybrid Gastric Cancer Exosome as Potential Drug Carrier for Targeted Gastric Cancer Therapy. J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.3167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Gastric cancer is among the leading lethal cancer types in the world. However, its five year survival rate is far from satisfactory. Therefore, the development of targeted cancer gastric cancer therapy is a promising way to cure gastric cancer. Gastric cancer exosome is reported to
have high caner targeting efficacy, but its yield is relatively low. Herein, we proposed a facile way to construct hybrid gastric cancer exosome (HGCE) with high yield as potential drug carrier for targeted gastric cancer therapy. The doxorubicin (Dox) loaded HGCE (Dox/HGCE) was developed
as drug delivery system (DDS) to treat gastric cancer. In vitro and in vivo results demonstrated that Dox/HGCE showed not only high and specific homing ability to the gastric cancer cells (SGC7901) but also good anticancer performance which can be a promising DDS for gastric
cancer therapy.
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Affiliation(s)
- Qing Tian
- Department of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050031, China
| | - Ying Guo
- Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050031, China
| | - Dan Li
- Department of Thoracic Surgery, Jingxing County Hospital, Shijiazhuang City, Hebei Province, 050030, China
| | - Liang Dong
- Department of Medical, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050031, China
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Formulation development and in vitro–in vivo anticancer potential of novel nanoliposomal fluorinated curcuminoids. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Sharifi S, Dalir Abdolahinia E, Ghavimi MA, Dizaj SM, Aschner M, Saso L, Khan H. Effect of Curcumin-Loaded Mesoporous Silica Nanoparticles on the Head and Neck Cancer Cell Line, HN5. Curr Issues Mol Biol 2022; 44:5247-5259. [PMID: 36354669 PMCID: PMC9688994 DOI: 10.3390/cimb44110357] [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: 09/16/2022] [Revised: 10/08/2022] [Accepted: 10/25/2022] [Indexed: 11/16/2022] Open
Abstract
Curcumin is an active ingredient isolated from Curcuma longa. It has several pharmacological effects, including anticancer, anti-inflammatory, and antioxidant effects. Due to its low bioavailability, chemical structure instability, and easy oxidation, the application of curcumin has been limited. In this study, to overcome these limitations, curcumin-loaded mesoporous silica nanoparticles (Cur-MSN) were prepared, and the anticancerous effect of Cur-MSNs on head and neck cancer cells, HN5, was investigated. Transmission electron microscopy (TEM) revealed rod-shaped mesoporous nanoparticles with average particle size smaller than 100 nm. Higher cytotoxicity of Cur-MSNs was seen in treated cancer cells compared with free curcumin. The expression of Bcl-2 was significantly reduced in the presence of Cur-MSNs compared to the control (untreated HN5 cells) (p < 0.05). A 3.43-fold increase in the Bax/Bcl-2 ratio was seen in Cur-MSNs treated HN5 cells at the IC50. Cur-MSNs increased intracellular reactive oxygen species (ROS) production. Based on these novel results, we suggest that Cur-MSNs offer efficacy for cancer treatment and future studies should further characterize their properties in various experimental cancer models.
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Affiliation(s)
- Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran
| | - Elaheh Dalir Abdolahinia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran
| | - Mohammad Ali Ghavimi
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran
| | - Solmaz Maleki Dizaj
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran
- Correspondence: (S.M.D.); (H.K.)
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine Forchheimer, Bronx, NY 10461, USA
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, 00185 Rome, Italy
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
- Correspondence: (S.M.D.); (H.K.)
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Preparation of nano-composites based on curcumin/chitosan-PVA-alginate to improve stability, antioxidant , antibacterial and anticancer activity of curcumin. INORG CHEM COMMUN 2022. [DOI: 10.1016/j.inoche.2022.110022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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44
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Venkatas J, Daniels A, Singh M. The Potential of Curcumin-Capped Nanoparticle Synthesis in Cancer Therapy: A Green Synthesis Approach. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:3201. [PMID: 36144994 PMCID: PMC9502936 DOI: 10.3390/nano12183201] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 09/05/2022] [Accepted: 09/09/2022] [Indexed: 06/16/2023]
Abstract
Cancer nanotherapeutics is an important field of research which utilizes nanomaterials as an approach to cancer therapy. Nano-mediated therapeutic delivery systems overcome the adverse side effects of traditional cancer treatment methods. Nanoparticles (NPs) are considered excellent tumor-targeting vehicles due to their compact and variable size, large surface area, ability to load several genes and drugs, and mediation of increased therapeutic payload uptake. Despite the rapid development of nanotechnology, there is growing concern regarding the possible long-term side effects of NPs on the environment and human health. Green chemistry using plant materials, such as curcumin, is a sustainable alternative to conventional reduction methods and confers dual reducing and capping properties. Curcumin is a bioactive compound isolated from the rhizome of the Curcuma longa plant, which exhibits various medicinal properties. Curcumin-capped NPs exhibit increased solubility, bioavailability, therapeutic indices, and antitumor properties. This review highlights the potential and antitumor properties of economical, simple, and eco-friendly curcumin-synthesized and capped NPs for the localized delivery of therapeutic genes and drugs to the cancer tumor microenvironment with fewer adverse side effects.
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Trendafilova I, Chimshirova R, Momekova D, Petkov H, Koseva N, Petrova P, Popova M. Curcumin and Capsaicin-Loaded Ag-Modified Mesoporous Silica Carriers: A New Alternative in Skin Treatment. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:3075. [PMID: 36080112 PMCID: PMC9458240 DOI: 10.3390/nano12173075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/27/2022] [Accepted: 08/28/2022] [Indexed: 06/15/2023]
Abstract
Biologically active substances of natural origin offer a promising alternative in skin disease treatment in comparison to synthetic medications. The limiting factors for the efficient application of natural compounds, such as low water solubility and low bioavailability, can be easily overcome by the development of suitable delivery systems. In this study, the exchange with the template procedure was used for the preparation ofa spherical silver-modified mesoporous silica nanocarrier. The initial and drug-loaded formulations are fully characterized by different physico-chemical methods. The incipient wetness impregnation method used to load health-promoting agents, curcumin, and capsaicin in Ag-modified carriers separately or in combinationresulted in high loading efficiency (up to 33 wt.%). The interaction between drugs and carriers was studied by ATR-FTIR spectroscopy. The release experiments of both active substances from the developed formulations were studied in buffers with pH 5.5, and showed improved solubility. Radical scavenging activity and ferric-reducing antioxidant power assays were successfully used for the evaluation of the antiradical and antioxidant capacity of the curcumin or/and capsaicin loaded on mesoporous carriers. Formulations containing a mixture of curcumin and capsaicin were characterized bypotentiation of their antiproliferative effect against maligning cells, and it was confirmed that the system for simultaneous delivery of both drugs has lower IC50 values than the free substances.The antibacterial tests showed better activity of the obtained delivery systems in comparison with the pure curcumin and capsaicin. Considering the obtained results, it can be concluded that the obtained delivery systems are promising for potential dermal treatment.
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Affiliation(s)
- Ivalina Trendafilova
- Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Ralitsa Chimshirova
- Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Denitsa Momekova
- Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria
| | - Hristo Petkov
- Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Neli Koseva
- Institute of Polymers, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Penka Petrova
- Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Margarita Popova
- Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
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Maleki Dizaj S, Sharifi S, Tavakoli F, Hussain Y, Forouhandeh H, Hosseiniyan Khatibi SM, Memar MY, Yekani M, Khan H, Goh KW, Ming LC. Curcumin-Loaded Silica Nanoparticles: Applications in Infectious Disease and Food Industry. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:nano12162848. [PMID: 36014710 PMCID: PMC9414236 DOI: 10.3390/nano12162848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/10/2022] [Accepted: 08/13/2022] [Indexed: 05/12/2023]
Abstract
Curcumin has multiple properties that are used to cure different diseases such as cancer, infections, inflammatory, arthritic disease, etc. Despite having many effects, the inherent physicochemical properties-such as poor water solubility, chemical instability, low bioavailability, photodegradation, fast metabolism, and short half-life-of curcumin's derivatives have limited its medical importance. Recently, unprecedented advances in biomedical nanotechnology have led to the development of nanomaterial-based drug delivery systems in the treatment of diseases and diagnostic goals that simultaneously enhance therapeutic outcomes and avoid side effects. Mesoporous silica nanoparticles (MSNs) are promising drug delivery systems for more effective and safer treatment of several diseases, such as infections, cancers, and osteoporosis. Achieving a high drug loading in MSNs is critical to the success of this type of treatment. Their notable inherent properties-such as adjustable size and porosity, high pore volume, large surface area, functionality of versatile surfaces, as well as biocompatibility-have prompted extraordinary research on MSNs as multi-purpose delivery platforms. In this review, we focused on curcumin-loaded silica nanoparticles and their effects on the diagnosis and treatment of infections as well as their use in food packaging.
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Affiliation(s)
- Solmaz Maleki Dizaj
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
| | - Simin Sharifi
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
- Correspondence: (S.S.); (H.K.)
| | - Fatemeh Tavakoli
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
| | - Yaseen Hussain
- Lab of Controlled Release and Drug Delivery System, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Haleh Forouhandeh
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
| | | | - Mohammad Yousef Memar
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
| | - Mina Yekani
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz 5165665931, Iran
- Department of Microbiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan 8715988141, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan 8715988141, Iran
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan
- Correspondence: (S.S.); (H.K.)
| | - Khang Wen Goh
- Faculty of Data Science and Information Technology, INTI International University, Nilai 78100, Malaysia
| | - Long Chiau Ming
- PAP Rashidah Sa’adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Bandar Seri Begawan BE 1410, Brunei
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Đoković JB, Demisli S, Savić SM, Marković BD, Cekić ND, Randjelovic DV, Mitrović JR, Lunter DJ, Papadimitriou V, Xenakis A, Savić SD. The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions. Pharmaceutics 2022; 14:pharmaceutics14081666. [PMID: 36015291 PMCID: PMC9415641 DOI: 10.3390/pharmaceutics14081666] [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: 06/28/2022] [Revised: 07/24/2022] [Accepted: 08/08/2022] [Indexed: 11/18/2022] Open
Abstract
A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions.
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Affiliation(s)
- Jelena B. Đoković
- Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
| | - Sotiria Demisli
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
- Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, Greece
| | | | - Bojan D. Marković
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
| | - Nebojša D. Cekić
- DCP Hemigal, Tekstilna 97, 16000 Leskovac, Serbia
- Department of Pharmaceutical Technology and Cosmetology, Faculty of Technology, University of Niš, Bulevar Oslobođenja 124, 16000 Leskovac, Serbia
| | - Danijela V. Randjelovic
- Department of Microelectronic Technologies, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia
| | - Jelena R. Mitrović
- Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
| | - Dominique Jasmin Lunter
- Institut für Pharmazeutische Technologie, Eberhard-Karls Universität, D-72076 Tübingen, Germany
| | | | - Aristotelis Xenakis
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece
| | - Snežana D. Savić
- Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
- Correspondence:
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Zhang Y, You C, Pei Y, Yang F, Li D, Jiang YZ, Shao Z. Integration of radiogenomic features for early prediction of pathological complete response in patients with triple-negative breast cancer and identification of potential therapeutic targets. Lab Invest 2022; 20:256. [PMID: 35672824 PMCID: PMC9171937 DOI: 10.1186/s12967-022-03452-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/20/2022] [Indexed: 12/28/2022]
Abstract
Background We established a radiogenomic model to predict pathological complete response (pCR) in triple-negative breast cancer (TNBC) and explored the association between high-frequency mutations and drug resistance. Methods From April 2018 to September 2019, 112 patients who had received neoadjuvant chemotherapy were included. We randomly split the study population into training and validation sets (2:1 ratio). Contrast-enhanced magnetic resonance imaging scans were obtained at baseline and after two cycles of treatment and were used to extract quantitative radiomic features and to construct two radiomics-only models using a light gradient boosting machine. By incorporating the variant allele frequency features obtained from baseline core tissues, a radiogenomic model was constructed to predict pCR. Additionally, we explored the association between recurrent mutations and drug resistance. Results The two radiomics-only models showed similar performance with AUCs of 0.71 and 0.73 (p = 0.55). The radiogenomic model had a higher predictive ability than the radiomics-only model in the validation set (p = 0.04), with a corresponding AUC of 0.87 (0.73–0.91). Two highly frequent mutations were selected after comparing the mutation sites of pCR and non-pCR populations. The MED23 mutation p.P394H caused epirubicin resistance in vitro (p < 0.01). The expression levels of γ-H2A.X, p-ATM and p-CHK2 in MED23 p.P394H cells were significantly lower than those in wild type cells (p < 0.01). In the HR repair system, the GFP positivity rate of MED23 p.P394H cells was higher than that in wild-type cells (p < 0.01). Conclusions The proposed radiogenomic model has the potential to accurately predict pCR in TNBC patients. Epirubicin resistance after MED23 p.P394H mutation might be affected by HR repair through regulation of the p-ATM-γ-H2A.X-p-CHK2 pathway. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-022-03452-1.
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Affiliation(s)
- Ying Zhang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui District, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Chao You
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.,Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Yuchen Pei
- Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Fan Yang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui District, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Daqiang Li
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui District, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Yi-Zhou Jiang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui District, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Zhimin Shao
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui District, Shanghai, People's Republic of China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
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Liposomal Nanoformulation as a Carrier for Curcumin and pEGCG—Study on Stability and Anticancer Potential. NANOMATERIALS 2022; 12:nano12081274. [PMID: 35457986 PMCID: PMC9028936 DOI: 10.3390/nano12081274] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 04/04/2022] [Accepted: 04/05/2022] [Indexed: 02/08/2023]
Abstract
Nanoformulations are regarded as a promising tool to enable the efficient delivery of active pharmaceutical ingredients to the target site. One of the best-known and most studied nanoformulations are liposomes—spherical phospholipid bilayered nanocarriers resembling cell membranes. In order to assess the possible effect of a mixture of polyphenols on both the stability of the formulation and its biological activity, two compounds were embedded in the liposomes—(i) curcumin (CUR), (ii) a peracetylated derivative of (−)-epigallocatechin 3-O-gallate (pEGCG), and (iii) a combination of the aforementioned. The stability of the formulations was assessed in two different temperature ranges (4–8 and 20 °C) by monitoring both the particle size and their concentration. It was found that after 28 days of the experiment, the liposomes remained largely unchanged in terms of the particle size distribution, with the greatest change from 130 to 146 nm. The potential decomposition of the carried substances was evaluated using HPLC. The combined CUR and pEGCG was sensitive to temperature conditions; however its stability was greatly increased when compared to the solutions of the individual compounds alone—up to 9.67% of the initial concentration of pEGCG in liposomes after 28 days storage compared to complete decomposition within hours for the non-encapsulated sample. The potential of the prepared formulations was assessed in vitro on prostate (LNCaP) and bladder cancer (5637) cell lines, as well as on a non-cancerous human lung fibroblast cell line (MRC-5), with the highest activity of IC50 equal 15.33 ± 2.03 µM for the mixture of compounds towards the 5637 cell line.
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