{"title":"Nanomaterials Mediated Enhancement of CAR-T for HCC: Revolutionizing Immunotherapy Strategies.","authors":"Xudong Liu, Ye Liu, Danyu Zhao, Dehong Shan, Chenghao Guo, Lianqun Jia","doi":"10.2147/IJN.S527315","DOIUrl":"10.2147/IJN.S527315","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) presents significant challenges due to its aggressive nature and resistance to conventional treatments. While CAR-T therapy has shown promise in hematologic cancers, its application in HCC is limited by the tumor microenvironment (TME), insufficient T-cell infiltration, and antigenic heterogeneity. Nanomaterials offer a promising solution by enhancing CAR-T cell delivery, activation, persistence, and overcoming the immunosuppressive TME. This review focuses on the application of nanoparticles in CAR-T therapy, highlighting recent advancements in nanomaterials-based mRNA delivery, photothermal remodeling, and hydrogel platforms. Furthermore, nanomaterials-enhanced imaging tools enable real-time monitoring of CAR-T cell activity, improving therapeutic precision and safety. By addressing current limitations, nanomaterial-mediated CAR-T therapy holds the potential to transform HCC treatment, paving the way for more effective and personalized cancer immunotherapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7489-7500"},"PeriodicalIF":6.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325656","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}
Vladimir Holan, Eliska Javorkova, Barbora Hermankova, Pavel Rossner
{"title":"Combined Therapy Using Mesenchymal Stem Cells and Metal Nanoparticles: Perspectives for Ocular Injuries and Diseases.","authors":"Vladimir Holan, Eliska Javorkova, Barbora Hermankova, Pavel Rossner","doi":"10.2147/IJN.S527928","DOIUrl":"10.2147/IJN.S527928","url":null,"abstract":"<p><p>Stem cell-based therapy represents a promising approach for the treatment of numerous currently uncurable diseases. However, wider application of this therapy is still bound by various limitations. To increase the effectiveness of cell therapy, a combined application of stem cells with various types of chemicals or agents, which could support the immunoregulatory and therapeutic properties of stem cells, has been proposed and tested. One prospective approach is offered by the co-application of mesenchymal stem cells (MSCs), which have potent immunomodulatory and regenerative properties, and selected metal nanoparticles (NPs) which have been used in various fields of medicine for their immunomodulatory, anti-oxidant and antibacterial properties. It has been shown that the main mechanism of the therapeutic action of MSCs is the production of immunomodulatory molecules and growth factors, and that the secretory activity of MSCs can be modified by different types of NPs. For this purpose, metal NPs are extremely useful. They possess unique characteristics and can influence the growth and repair of tissues, exert strong antimicrobial activity and serve as nanocarriers. Thus, treatment based on the simultaneous application of MSCs and selected NPs combines the therapeutic effects of MSCs and impacts of NPs on applied MSCs, and on the cells and tissues of the recipient. In this review we outline the current state of studies combining the administration of MSCs and the application of metal NPs, with a focus on perspectives to use such treatment for corneal and retinal injuries and diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7403-7414"},"PeriodicalIF":6.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316797","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":"Multi-Focused Acoustic Radiation Force Impulse Modulation of Murine Hepatic Xenografts Enhances Nanoscale DOX@Lip Delivery and Therapeutic Effect.","authors":"Size Wu, Chengfang Wang","doi":"10.2147/IJN.S522247","DOIUrl":"10.2147/IJN.S522247","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether multi-focused acoustic radiation force impulse (MF-ARFI) applied to murine xenograft liver tumors prior to intravenous administration of doxorubicin-loaded PEGylated liposomes (DOX@Lip) can enhance drug delivery efficiency through modulating the enhanced permeation and retention effect of the tumor, reduce side effects, and improve antitumor effect.</p><p><strong>Materials and methods: </strong>DOX@Lip and tumor-mimetic matrices were synthesized and characterized. Huh-7 cells and DOX@Lip were exposed to MF-ARFI and observed. MF-ARFI was applied to both tumor-mimetic matrices and saline with DOX@Lip to assess displacement effects. Subsequently, murine xenograft models were established and underwent MF-ARFI preconditioning before DOX@Lip injection. Tumor volume dynamics and body weight changes were longitudinally monitored. Terminal assessments included histopathology (H&E), apoptosis (TUNEL), and molecular profiling (BCL-2 and BAX by Western blot) of tumors and major organs.</p><p><strong>Results: </strong>There was no significant difference in the live/dead cell staining results between the Huh7 cells with and without MF-ARFI. There was no significant difference in cell apoptosis rates of Huh7 cells between DOX@Lip and DOX@Lip+MF-ARFI. MF-ARFI exposure induced measurable displacement of DOX@Lip in both tumor-mimetic matrices and saline. Mice receiving combined DOX@Lip and MF-ARFI treatment exhibited significantly attenuated tumor growth (p<0.05) and slight weight loss, which were significantly different from DOX and DOX+MF-ARFI treatments. Cardiac histopathology revealed no significant differences in myocardial toxicity between DOX@Lip and DOX@Lip+MF-ARFI groups relative to PBS controls. Conversely, tumors from the DOX@Lip+MF-ARFI group demonstrated distinct histopathological alterations compared to other groups. TUNEL staining results indicated a relatively higher level of cell apoptosis in mice treated with DOX@Lip+MF-ARFI. Molecular analyses showed MF-ARFI pretreatment significantly reduced BCL-2 expression (p<0.05) while elevating the BAX/BCL-2 ratio versus DOX@Lip monotherapy.</p><p><strong>Conclusion: </strong>Preconditioning xenograft tumors with MF-ARFI prior to DOX@Lip administration faciliates DOX@Lip delivery and significantly enhances antitumor effect while reducing cardiotoxicity. This combinatorial strategy demonstrates translational potential for optimizing liposomal chemotherapeutic delivery and effect.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7359-7373"},"PeriodicalIF":6.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316799","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}
Anam Anjum, Alvin Man Lung Chan, Hafiz Bilawal Hussain, Yogeswaran Lokanathan
{"title":"Advanced Therapeutic Approaches Based on Small Extracellular Vehicles (sEVs) For the Regeneration of Spinal Cord Injuries.","authors":"Anam Anjum, Alvin Man Lung Chan, Hafiz Bilawal Hussain, Yogeswaran Lokanathan","doi":"10.2147/IJN.S522028","DOIUrl":"10.2147/IJN.S522028","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is severe damage to part of the central nervous system (CNS) that can result in impaired sensory and motor function, significantly impacting the quality of life for patients and creating a substantial economic burden on society. The process of SCI involves both primary and secondary injury, with the latter being a series of heightened responses triggered by the initial damage. The complex nature of SCI's pathological mechanisms has made it challenging to develop effective treatment strategies in clinical settings. Small extracellular vesicles (sEVs) are membrane-bound vesicles with a size range of ≤200 nm, released from cells into extracellular spaces. These vesicles are heterogeneous and can originate from various intracellular compartments, including endosomal and non-endosomal sources. A growing body of evidence points to the potential of sEVs in repairing SCI. This review explores the preparation, functions, routes of administration, advantages, challenges, and advanced therapies for sEVs. It also examines the mechanisms through which various types of sEVs can promote healing in SCI and assesses the effectiveness of combining sEVs with other treatment approaches. Furthermore, the review discusses the opportunities and obstacles associated with using sEVs to repair SCI.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7415-7442"},"PeriodicalIF":6.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316795","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":"Nano-Biomimetic Fibronectin/Lysostaphin-Co-Loaded Silk Fibroin Dressing Accelerates Full-Thickness Wound Healing via ECM-Mimicking Microarchitecture and Dual-Function Modulation.","authors":"Chen-Ting Liu, Li-Dan Huang, Kai Liu, Ke-Fan Pang, Hao Tang, Ting Li, Yang-Pei Huang, Wei-Qin Zhang, Jun-Juan Wang, Guo-Li Yin, Kou-Zhen Hua","doi":"10.2147/IJN.S521956","DOIUrl":"10.2147/IJN.S521956","url":null,"abstract":"<p><strong>Purpose: </strong>In cases of large-area skin defects, the absence of extracellular matrix can lead to difficulties in fibroblast migration, thereby hindering wound healing. This study aimed to address the challenges in treating skin defects by developing a biomimetic nano-dressing that both has antibacterial properties and promotes healing by mimicking the extracellular matrix.</p><p><strong>Patients and methods: </strong>The electrospun silk protein nanofibers were ultrasonically fragmented into staple fibers. These were then coated and modified by adding a collagen (Col) solution loaded with recombinant lysostaphin (rLys) and fibronectin (Fn), ultimately constructing a biomimetic nanosponge (Fn-rLys-Col/SF-S).</p><p><strong>Results: </strong>In vitro studies have shown that Fn-rLys-Col/SF-S possesses good water vapor balance and antibacterial properties, is non-toxic to cells, and can promote cell proliferation and migration. In vivo experimental results indicated that Fn-rLys-Col/SF-S healed a week earlier than the control group, with the structure of the newly formed skin resembling normal skin at 21 days. Further immunohistochemistry and qRT-PCR results demonstrated that Fn-rLys-Col/SF-S effectively promotes the healing of skin defect wounds by reducing inflammation, promoting angiogenesis, enhancing collagen deposition, and regulating the degree of fibrosis.</p><p><strong>Conclusion: </strong>In conclusion, the Fn-rLys-Col/SF-S biomimetic sponge dressing can promote the repair of skin defects by mimicking the extracellular matrix, providing a potential therapeutic strategy for clinical wound treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7469-7487"},"PeriodicalIF":6.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316800","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":"Diverse-Origin Exosomes Therapeutic Strategies for Diabetic Wound Healing.","authors":"Fengyu Wang, Jinling Yao, Huiling Zuo, Yuhang Jiao, Junzi Wu, Zhuoran Meng","doi":"10.2147/IJN.S519379","DOIUrl":"10.2147/IJN.S519379","url":null,"abstract":"<p><p>Diabetic wounds represent a pressing clinical challenge in the medical field. Compared to healthy individuals, patients with diabetes present with various complications, including abnormal blood sugar levels, microcirculation disorders, and impaired cellular function. Moreover, they are at a higher risk for skin damage and have a more difficult healing process. In recent years, exosome-based regenerative medicine has provided new strategies for diabetic wound treatment. The bioactive molecules contained in the exosomes, including functional proteins, bioactive lipids, and regulatory RNAs, allow them to suppress inflammation, enhance cell migration, and promote angiogenesis. As exosomes from different sources have different composition and function, the characteristics of their source must be considered when using them. Unlike traditional single source research, this review describes the mechanism of action of exosomes from different sources in diabetic wound-healing process, including mammalian cell-derived exosomes and plant-derived exosome-like nanoparticles. These findings not only provide a theoretical basis for the selection of exosome sources but also lay a foundation for the development of personalized, multimodal treatment plans.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7375-7402"},"PeriodicalIF":6.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316798","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":"Cancer-Derived Exosomal LINC01615 Induces M2 Polarization of Tumor-Associated Macrophages via RBMX-EZH2 Axis to Promote Colorectal Cancer Progression.","authors":"Anshu Li, Jiaxin Hong, Xianxiong Ma, Yongzhou Huang, Qi Jiang, Chenggang Zhang, Yu Wang, Yongming Huang","doi":"10.2147/IJN.S499381","DOIUrl":"10.2147/IJN.S499381","url":null,"abstract":"<p><strong>Background: </strong>LncRNAs have been proved to play an important role in human cancers. The M2 polarization of tumor associated macrophages (TAMs) is also reported to promote cancer progression. However, the specific role of cancer derived exosomal lncRNA in the M2 polarization of macrophages remains largely unknown.</p><p><strong>Methods: </strong>Bioinformatic analysis was used to screen out the differentially expressed lncRNAs in colorectal cancer (CRC). Single-cell RNA sequencing was conducted to investigate the different distribution of cell type in tumor and para-tumor tissues. Function gain and loss assays were performed both in vitro and in vivo to verify the specific role of target genes. The involvement of exosomes was verified by transmission electron microscopy, nano-sight particle tracking analysis and Cre-LoxP system. RNA immunoprecipitation, RNA pull-down, truncation experiment, dual-luciferase reporter assay, chromatin immunoprecipitation, qRT-PCR and Western blot were used to explore the interactions between LINC01615, RBMX and EZH2.</p><p><strong>Results: </strong>LINC01615 was highly expressed in CRC and contributed to the M2 polarization of TAMs and progression of CRC. Mechanistically, LINC01615 could be transported from CRC cells to TAMs via exosomes. The exosomal LINC01615 acted as a scaffold to mediate the combination between RBMX and EZH2 mRNA and EZH2 promoter, which promoted EZH2 expression and M2 polarization of TAMs, thus promoting CRC progression.</p><p><strong>Conclusion: </strong>Cancer-derived exosomal LINC01615 induces M2 polarization of TAMs via RBMX-EZH2 axis to promote CRC progression, which may be a reliable diagnostic marker and potential therapeutic target for CRC.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7343-7358"},"PeriodicalIF":6.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316796","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":"Multifaceted Applications of Nanomaterials in Colorectal Cancer Management: Screening, Diagnostics, and Therapeutics.","authors":"He Xin, Zhihui Chang, Meng Niu","doi":"10.2147/IJN.S520616","DOIUrl":"10.2147/IJN.S520616","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Early detection and treatment of CRC can significantly improve patient survival and quality of life, while advanced-stage patients still face numerous challenges, such as drug resistance and adverse effects. Consequently, researchers are developing more efficient early screening and diagnostic strategies for CRC. Consequently, researchers are actively developing more efficient strategies for diagnosis and refined treatments. This review comprehensively examines the diverse applications of various nanomaterials in CRC management, including screening, diagnostic imaging, surgical guidance, drug delivery, radiotherapy, and modulation of the tumor microenvironment. Firstly, we explored how nanomaterials are revolutionizing CRC screening by enhancing the detection of early-stage tumors. In the realm of diagnostic imaging, nanomaterials are employed to improve the clarity and specificity of imaging modalities, thereby facilitating more accurate diagnoses. The review also examines the use of nanomaterials in surgical guidance, where they aid in the precise identification and removal of tumors, potentially improving surgical outcomes. Furthermore, the review underscores the significance of nanomaterials in drug delivery systems, which enable targeted therapy and reduce systemic side effects. We also discussed the role of nanomaterials in radio-sensitization, where they enhance the efficacy of radiotherapy by increasing the sensitivity of tumor cells to radiation. Additionally, the modulation of the tumor immune microenvironment using nanomaterials is highlighted as a promising strategy to induce immune response against cancer cells. Throughout the review, the mechanisms of action of these nanomaterials are meticulously examined, providing insights into how they interact with biological systems to achieve their therapeutic effects. The efficacy of these nanomaterials in overcoming drug resistance is also a focal point, as this is a critical factor in improving the long-term outcomes for CRC patients. In conclusion, while nanomaterials hold great promise for the management of CRC, addressing their biocompatibility and clinical translation challenges is crucial for their safe and effective application in clinical settings.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7271-7294"},"PeriodicalIF":6.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302086","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}
Jianlin Shen, Wenying Bin, Xiaoning Lin, Yue Lai, Xuan Lin, Taiyuan Guan, Huan Liu
{"title":"Klotho Protein: A Multifaceted Guardian of Healthy Aging and Its Therapeutic Potential.","authors":"Jianlin Shen, Wenying Bin, Xiaoning Lin, Yue Lai, Xuan Lin, Taiyuan Guan, Huan Liu","doi":"10.2147/IJN.S514516","DOIUrl":"10.2147/IJN.S514516","url":null,"abstract":"<p><p>The Klotho protein, encoded by the KL gene, has garnered significant attention as a pivotal biomolecule in the field of aging research. Its expression levels are closely correlated with both lifespan and overall health status, exerting influence over critical physiological processes such as metabolic homeostasis, oxidative stress response, and inflammation modulation. This review aims to systematically examine the multifaceted roles of Klotho within the context of aging and its implications for various age-associated disorders. We highlight the emerging evidence suggesting that Klotho may serve as a key regulator in age-related pathologies, including cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Furthermore, we explore the potential of Klotho as a therapeutic target, positing that interventions aimed at enhancing Klotho activity could offer novel strategies for alleviating the health burdens experienced by the aging population.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7251-7270"},"PeriodicalIF":6.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302075","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":"Liposomal Nanoparticle Delivery of Ginkgo Flavone Glycosides Enhances SIRT1 Activation and Improves Diabetic Cardiomyopathy.","authors":"Wei Gao, Ruoran Chen, Huixin Tong, Yu Wang, Linlang Liang, Yiyao Li, Hao Yu","doi":"10.2147/IJN.S493862","DOIUrl":"10.2147/IJN.S493862","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the therapeutic mechanisms of Ginkgo Flavone Glycosides (GFGs) delivered via liposomal nanoparticles in treating Diabetic Cardiomyopathy (DCM) by upregulating Sirtuin 1 (SIRT1) to restore energy metabolism and autophagy homeostasis.</p><p><strong>Methods: </strong>A DCM mouse model was employed, with groups treated with different doses of GFGs. Various evaluations, including body weight, blood glucose levels, and cardiac function, were performed. Network pharmacology, transcriptomic analysis, and molecular docking studies were conducted to elucidate the key role of SIRT1 in inhibiting DCM progression. In vitro experiments and proteomic sequencing were utilized to validate the regulatory effects of SIRT1.</p><p><strong>Results: </strong>The in vivo animal experiment results demonstrated that treatment with Ginkgo Flavone Glycosides (GFGs) significantly improved cardiac function in diabetic cardiomyopathy mice. Specifically, GFG treatment increased the left ventricular ejection fraction (LVEF) by approximately 81.3% compared to the Model+Lipo group, reduced the left ventricular internal diameter in systole (LVIDs) by approximately 69.2%, and decreased the left ventricular internal diameter in diastole (LVIDd) thickness by approximately 56.1%. Additionally, GFGs alleviated cardiomyocyte apoptosis, further supporting their therapeutic potential for diabetic cardiomyopathy. Bioinformatics analysis supported the regulation of DCM through the SIRT1/FOSL1/TSPAN4 axis. Proteomic data confirmed the beneficial effects of GFGs on diabetic cardiac energy metabolism and autophagy. Liposomal nanoparticles loaded with GFGs significantly extended drug release to 72 hours. In vitro experiments highlighted the role of SIRT1 in modulating FOSL1 and TSPAN4 expression. Proteomic sequencing further validated the regulatory role of the SIRT1/FOSL1/TSPAN4 signaling pathway in DCM and suggested that GFGs might enhance energy metabolism and autophagy in diabetic hearts by activating SIRT1.</p><p><strong>Conclusion: </strong>Liposomal nanoparticle delivery of GFGs was shown to enhance SIRT1 activation, leading to the deacetylation of FOSL1 and suppression of TSPAN4, ultimately improving energy metabolism and autophagy in DCM. This study introduces a novel potential strategy for the treatment of DCM.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"7295-7321"},"PeriodicalIF":6.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302085","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}