International Journal of Nanomedicine最新文献

{"title":"Response to Article \"Ultrasensitive Hierarchical AuNRs@SiO₂@Ag SERS Probes for Enrichment and Detection of Insulin and C-Peptide in Serum\" [Letter].","authors":"Subash C B Gopinath","doi":"10.2147/IJN.S502364","DOIUrl":"10.2147/IJN.S502364","url":null,"abstract":"","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Antigen-Tethered Spiked Virus-Like- Poly(Lactic-Co-Glycolic Acid)-Nanoparticle Vaccine Enhances Antitumor Ability Through Th9 Promotion in Mice.","authors":"Ting-Wei Lin, Po-Yu Chou, Yen-Ting Shen, Ming-Thau Sheu, Kuo-Hsiang Chuang, Shyr-Yi Lin, Chia-Yi Chang","doi":"10.2147/IJN.S476715","DOIUrl":"10.2147/IJN.S476715","url":null,"abstract":"<p><strong>Purpose: </strong>Immunotherapy emerges as a promising frontier in cancer therapy and prevention. This study investigates the capacity of tumor-antigenic nanoparticles, specifically ovalbumin-tethered spiked virus-like poly(lactic-co-glycolic acid) nanoparticles (OVA-sVLNP), to effectively elicit humoral and cellular immune responses against tumors.</p><p><strong>Methods: </strong>OVA-sVLNP were synthesized through thiol-maleimide crosslinking using a single emulsion method. Comprehensive characterization was performed through Nuclear Magnetic Resonance (NMR), dynamic light scattering, Cryo-electron microscopy (Cryo-EM), confocal microscopy, and flow cytometry. Immunogenicity was evaluated using an enzyme-linked immunosorbent assay (ELISA) for quantifying immunoglobulin levels (IgG, IgG1, IgG2a) and cytokines in mouse sera. Flow cytometry profiled cellular immune responses in mouse spleens, and organ biosafety was assessed using immunohistochemistry and hematoxylin and eosin (H&E) staining.</p><p><strong>Results: </strong>OVA-sVLNP had a mean particle size of 193.8 ± 11.9 nm, polydispersity index of 0.307 ± 0.04, and zeta potential of -39.6 ± 10.16 mV, remaining stable for one month at 4°C. In vitro studies revealed significant upregulation of CD80/CD86 in dendritic cells, indicating robust activation. In vivo, the optimal concentration (V25) induced potent IgG, IgG1, and IgG2a antibodies, significant populations of CD3⁺CD4⁺, CD3⁺CD8⁺, and a rare subset of CD3⁺CD4⁺CD8⁺ memory T cells. Notably, Th9 induction resulted in the secretion of IL-9, IL-10, and other cytokines, which are crucial for orchestrating cytotoxic T cell activity and antitumor effects. Overall, higher doses did not improve outcomes, highlighting the significance of optimal dosing.</p><p><strong>Conclusion: </strong>This study demonstrated potent immunogenicity of OVA-sVLNP, characterized by the induction of specific IgG antibodies and the stimulation of cellular immune responses, particularly tumor-killing Th9 cells. The simplicity and cost-effectiveness of the manufacturing process augment the potential of OVA-sVLNP as a viable candidate for antitumor vaccines, opening new avenues for cancer prevention and cell-based therapeutic strategies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nebulization of Hypoxic hUCMSC-EVs Attenuates Airway Epithelial Barrier Defects in Chronic Asthma Mice by Transferring CAV-1.","authors":"Xinkai Luo, Ying Wang, Yufei Mao, Xiaowei Xu, Weifeng Gu, Wen Li, Chaoming Mao, Tingting Zheng, Liyang Dong","doi":"10.2147/IJN.S476151","DOIUrl":"10.2147/IJN.S476151","url":null,"abstract":"<p><strong>Background: </strong>Nebulization of hypoxic human umbilical cord mesenchymal stem cell-derived extracellular vesicles (Hypo-EVs) can suppress airway inflammation and remodeling in a chronic asthmatic mouse; however, the exact mechanism remains unclear. Recently, airway epithelial barrier defects have been regarded as crucial therapeutic targets in asthma. The aim of this study was to investigate whether and how Hypo-EVs protect against the disruption of the airway epithelial barrier under asthmatic conditions.</p><p><strong>Methods: </strong>The therapeutic effects of Hypo-EVs on airway epithelial barrier defects were evaluated in ovalbumin (OVA)-induced asthmatic mice and in IL-4 and IL-13-induced HBE135-E6E7 cell models by detecting cell monolayer leakage and junctional protein expression. The protein levels in Hypo-EVs were determined by Western blotting, and a gene knockdown approach was used to investigate the biofactors in Hypo-EVs.</p><p><strong>Results: </strong>Nebulization of Hypo-EVs directly alleviated airway epithelial barrier defects in asthmatic mice, as evidenced by colocalization with bronchial epithelial cells, decreased albumin concentration, and increased ZO-1 and E-cadherin expression. In vitro, Hypo-EV treatment dramatically rescued the increase in airway cell permeability, and upregulated the ZO-1 and E-cadherin protein expressions. Based on WB analysis, we found that caveolin-1 (CAV-1) was strongly enriched in Hypo-EVs. The knockdown of CAV-1 protein levels in Hypo-EVs significantly impaired Hypo-EV-mediated barrier protection in vitro and in vivo. Moreover, CAV-1 knockdown significantly abolished the beneficial effects of Hypo-EVs on airway inflammation and remodeling in asthmatic mice. In addition, we showed that IL-4/IL-13-induced airway epithelial barrier defects were mainly related to activation of STAT6 phosphorylation (p-STAT6), and overexpression of CAV-1 or Hypo-EV treatment inhibited the levels of p-STAT6 in IL-4/IL-13-induced HBE135-E6E7 cells.</p><p><strong>Conclusion: </strong>Nebulization of Hypo-EVs can attenuate airway epithelial barrier defects in asthma by delivering CAV-1 to inhibit p-STAT6 expression and may be used to treat other barrier defect diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Oral Nanoparticle-Encapsulated Insulin in Reducing Oxidative Stress and Enhancing Tissue Integrity in a Diabetic Rat Model.","authors":"Nawel Kaddour, Farah Benyettou, Kawtar Moulai, Abdelouahab Mebarki, Rose Ghemrawi, Zine-Charaf Amir, Hafida Merzouk, Ali Trabolsi, Nassima Amel Mokhtari-Soulimane","doi":"10.2147/IJN.S468756","DOIUrl":"10.2147/IJN.S468756","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus, a chronic metabolic disorder, leads to systemic organ damage characterized by oxidative stress and structural alterations, contributing to increased morbidity and mortality. Traditional subcutaneous insulin therapy, while managing hyperglycemia, often falls short in addressing the oxidative damage and preventing organ-specific complications. This study evaluates the therapeutic efficacy of a novel oral nanoparticle-mediated insulin (nCOF/Insulin) against these diabetes-induced changes, comparing it with traditional subcutaneous insulin in a streptozotocin (STZ)-induced diabetic rat model.</p><p><strong>Methods: </strong>We induced diabetes in Wistar rats, dividing them into four groups: standard control, diabetic control, diabetic treated with subcutaneous insulin, and diabetic treated with oral nanoparticle-mediated insulin (nCOF/Insulin). Assessments included organ and body weights, histopathological examinations, and oxidative stress markers (MDA and PCOs) across various organs, including the brain, muscle, intestine, spleen, heart, liver, kidney, and adrenal glands. Additionally, we evaluated antioxidant parameters (GSH and catalase) and conducted immunohistochemical analysis of E-cadherin to assess intestinal integrity.</p><p><strong>Results: </strong>Our findings reveal that STZ-induced diabetes significantly impacts organ health, with subcutaneous insulin providing limited mitigation and, in some cases, exacerbating oxidative stress. Conversely, oral nCOF/Insulin treatment effectively restored organ and body weights, reduced oxidative stress markers, and mitigated histological damage. This suggests that oral nCOF/Insulin not only offers superior glycemic control but also addresses the underlying oxidative stress.</p><p><strong>Conclusion: </strong>nCOF/Insulin emerges as a promising treatment for diabetes, with the potential to improve patient quality of life by ameliorating oxidative stress and preventing organ-specific complications. This study underscores the need for further investigation into the long-term effects and mechanisms of action of oral nCOF/Insulin, aiming to revolutionize diabetes management and treatment strategies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Probiotics for Diabetes Management: Advances, Challenges, and Future Directions in Translational Microbiology.","authors":"Shenghao Zhang, Jiahui Ma, Yilei Ma, Jia Yi, Beier Wang, Hanbing Wang, Qinsi Yang, Kun Zhang, Xiaoqing Yan, Da Sun, Jinfeng You","doi":"10.2147/IJN.S492651","DOIUrl":"10.2147/IJN.S492651","url":null,"abstract":"<p><strong>Background: </strong>Diabetes Mellitus (DM) is a substantial health concern worldwide, and its incidence is progressively escalating. Conventional pharmacological interventions frequently entail undesirable side effects, and while probiotics offer benefits, they are hindered by constraints such as diminished stability and effectiveness within the gastrointestinal milieu. Given these complications, the advent of bioengineered probiotics is a promising alternative for DM management.</p><p><strong>Aim of review: </strong>The objective of this review is to provide an exhaustive synthesis of the most recent studies on the use of engineered probiotics in the management of DM. This study aimed to clarify the mechanisms through which these probiotics function, evaluate their clinical effectiveness, and enhance public awareness of their prospective advantages in the treatment of DM.</p><p><strong>Key scientific concepts of review: </strong>Scholarly critiques have explored diverse methodologies of probiotic engineering, including physical alteration, bioenrichment, and genetic manipulation. These techniques augment the therapeutic potency of probiotics by ameliorating gut microbiota, fortifying the intestinal barrier, modulating metabolic pathways, and regulating immune responses. Such advancements have established engineered probiotics as a credible therapeutic strategy for DM, potentially providing enhanced results compared to conventional treatments.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-in-One Nanozyme for Radiosensitization of Bladder Cancer.","authors":"Yang Li, Yuhan Zhang, Na Feng, Fan Yu, Bin Liu","doi":"10.2147/IJN.S463242","DOIUrl":"10.2147/IJN.S463242","url":null,"abstract":"<p><strong>Purpose: </strong>Bladder cancer is a common malignancy of the urinary system and the development of noninvasive therapeutic methods is imperative to avoid radical cystectomy, which results in a poor quality of life for patients.</p><p><strong>Methods: </strong>In this study, ultrasmall copper-palladium nanozymes decorated with cysteamine (CPC) nanoparticles (NPs) were synthesized to enhance the efficacy of radiotherapy (RT) in treating bladder cancer. CPC NPs react with intracellular overexpressed H₂O₂ in the tumor microenvironment to produce large quantities of reactive oxygen species (ROS) and induce tumor cell apoptosis. Furthermore, the CPC nanozymes can generate ample oxygen within tumors by utilizing H₂O₂, addressing hypoxia conditions, and mitigating radioresistance. Additionally, CPC facilitates the oxidation of glutathione (GSH) into oxidized glutathione disulfide (GSSG), blocking the self-repair mechanisms of tumor cells post-treatment. Simultaneously, CPC enhances the ionization energy deposition effect on tumor cells.</p><p><strong>Results: </strong>The results demonstrate an increased level of ROS and an elevation in oxygen content at the tumor site. Importantly, tumor growth was restrained without apparent systemic toxicity during the combined treatment.</p><p><strong>Conclusion: </strong>In summary, this study highlights the potential of CPC nanozyme-mediated radiotherapy as a promising avenue for the effective treatment of bladder cancer and demonstrates its potential for future clinical applications in the synergistic therapy of bladder cancer.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKH Dyes Should Be Avoided in the EVs Biodistribution Study of the Brain: A Call for Caution.","authors":"Zheng Wan, Tianyi Liu, Ning Xu, Wenhao Zhu, Xiaoyu Zhang, Qin Liu, Haifeng Wang, Honglei Wang","doi":"10.2147/IJN.S475060","DOIUrl":"10.2147/IJN.S475060","url":null,"abstract":"<p><strong>Introduction: </strong>Extracellular vesicles (EVs) are nanosized membrane vesicles that are naturally secreted by almost all cells and have gained considerable attention. Many studies have applied EVs to the treatment of brain diseases and validated their effectiveness. Although only a few EVs can penetrate the blood‒brain barrier (BBB) into the brain after administration, it has been proven that EVs and their cargos exert their effects by interacting with brain cells. PKH dyes are commonly used to stain EVs for distribution studies. However, systematic investigations of imaging characteristics of the PKH-labeled EVs distributed in the brain are still scarce.</p><p><strong>Methods: </strong>We stained EVs derived from mesenchymal stem cells with PKH26 or PKH67. PKH26-labeled EVs and PKH67-labeled EVs were administered at the same time into each mouse while PKH26-labeled EVs were given through tail veins and PKH67-labeled EVs were given through intraperitoneal injection. Confocal microscopy was used to explore the distribution difference of two types of EVs given via different routes in the brain.</p><p><strong>Results: </strong>The fluorescence of PKH26 and PKH67 had nearly identical distributions in brain slices after 1 h, 6 h, 12 h and 1 day of EV administration. Under the same confocal parameters, brain slices without EVs administration demonstrated the same result. However, liver slices from mice administered with labeled EVs showed obviously different distributions of two types PKH fluorescence.</p><p><strong>Discussion: </strong>These findings raise questions about the ability of PKH dyes as labels for EVs when explore the EV brain distribution observed via confocal microscopy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Carbon Nanomaterials to Enhancing Tumor Immunotherapy: Current Advances and Prospects.","authors":"Yun Li, Zhijie Xu, Zijuan Qi, Xiaofeng Huang, Mingyu Li, Sijin Liu, Yuanliang Yan, Ming Gao","doi":"10.2147/IJN.S480799","DOIUrl":"10.2147/IJN.S480799","url":null,"abstract":"<p><p>Recent advances in tumor immunotherapy have highlighted the pivotal role of carbon nanomaterials, such as carbon dots, graphene quantum dots, and carbon nanotubes. This review examines the unique benefits of these materials in cancer treatment, focusing on their mechanisms of action within immunotherapy. These include applications in immunoregulation, recognition, and enhancement. We explore how these nanomaterials when combined with specific biomolecules, can form immunosensors. These sensors are engineered for highly sensitive and specific detection of tumor markers, offering crucial support for early diagnosis and timely therapeutic interventions. This review also addresses significant challenges facing carbon nanomaterials in clinical settings, such as issues related to long-term biocompatibility and the hurdles of clinical translation. These challenges require extensive ongoing research and discussion. This review is of both theoretical and practical importance, aiming to promote using carbon nanomaterials in tumor immunotherapy, potentially transforming clinical outcomes and enhancing patient care.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the Thrombocytopenia Adverse Reaction of Belinostat Using Human Serum Albumin Nanoparticles.","authors":"Jia-Yu Liu, Chia-Hung Yen, Ya-Fan Lin, Yin-Hsun Feng, Yi-Ping Fang","doi":"10.2147/IJN.S475823","DOIUrl":"https://doi.org/10.2147/IJN.S475823","url":null,"abstract":"<p><strong>Background: </strong>Belinostat, a histone deacetylase inhibitor used for hematological cancer treatments, however, it caused thrombocytopenia, poor solubility, and rapid clearance. To mitigate these issues, human serum albumin (HSA) was utilized as the core material for its high protein binding affinity and self-binding capabilities. The study focused on developing belinostat-loaded HSA nanoparticles to improve solubility, extend circulation time, and reduce adverse effects.</p><p><strong>Methods: </strong>Belinostat-loaded HSA nanoparticles were synthesized using a desolvation method, optimized for size, charge, and entrapment efficiency, and characterized by molecular docking and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity was assessed in vitro against HuT-78 cells, and in vivo pharmacokinetics and toxicology studies were conducted to evaluate therapeutic efficacy and safety.</p><p><strong>Results: </strong>The prepared belinostat-HSA nanoparticles exhibited the size of 150 nm with a charge of ~-50 mV and a high entrapment efficiency (90%). Molecular docking confirmed that belinostat and HSA had a strong binding affinity (-9.5 kcal mol^-1), and the entrapment of belinostat within HSA nanoparticles was also confirmed via FTIR. Belinostat-HSA nanoparticles were cytotoxic against HuT-78 with the dose-response relation (1-100 μM). The highly concentrated (100 μM) belinostat-HSA nanoparticles maintained the viability of the peripheral blood mononuclear cells with 50% survival, which did not survive when exposed to belinostat (100 μM). The belinostat-HSA nanoparticles proved suitable for intravenous administration without causing hemolysis, exhibited prolonged circulation times, and improved in vivo platelet counts significantly (p < 0.05).</p><p><strong>Conclusion: </strong>In conclusion, the belinostat-loaded HSA nanoparticles significantly enhance the solubility and half-life of belinostat, reduce its adverse hematological effects, and maintain sustained drug release. These attributes underscore the potential of belinostat-HSA nanoparticles as a viable intravenous option for the treatment of hematological malignancies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyoxometalates Ameliorate Metabolic Dysfunction-Associated Steatotic Liver Disease by Activating the AMPK Signaling Pathway.","authors":"Dandan Wang, Jingguo Wang, Zequn Yin, Ke Gong, Shuang Zhang, Zhengbao Zha, Yajun Duan","doi":"10.2147/IJN.S485084","DOIUrl":"10.2147/IJN.S485084","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disorder, has garnered increasing attention globally owing to its associated health complications. However, the lack of available therapeutic medications and inadequate management of complications in metabolic dysfunction-associated steatohepatitis (MASH) present significant challenges. There are little studies evaluating the effectiveness of POM in treating MASLD. In this study, we synthesized polyoxometalates (POM) for potential treatment of MASLD.</p><p><strong>Methods: </strong>We induced liver disease in mice using two approaches: feeding a high-fat diet (HFD) to establish MASLD or feeding a methionine-choline deficient (MCD) diet to induce hepatic lipotoxicity and MASH. Various metabolic parameters were detected, and biochemical and histological evaluations were conducted on MASLD. Western blotting, qRT-PCR and immunofluorescence assays were used to elucidate the molecular mechanism of POM in the treatment of MASLD.</p><p><strong>Results: </strong>POM therapy resulted in significant improvements in weight gain, dyslipidemia, liver injury, and hepatic steatosis in mice fed a HFD. Notably, in a more severe dietary-induced MASH model with MCD diet, POM significantly attenuated hepatic lipid accumulation, inflammation, and fibrosis. POM treatment effectively attenuated palmitic acid and oleic acid-induced lipid accumulation in HepG2 and Huh7 cells by targeting the AMPK pathway to regulate lipid metabolism, which was confirmed by AMPK inhibitor. Additionally, the activation of AMPK signaling by POM suppressed the expression of lipid synthesis genes, including sterol regulatory element-binding protein 1c (SREBP1c) and SREBP2, while concurrently upregulating the expression of sirtuin 1 (SIRT1) to promote fatty acid oxidation.</p><p><strong>Conclusion: </strong>These findings suggest that POM is a promising therapeutic strategy with high efficacy in multiple MASLD models.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}