International Journal of Nanomedicine最新文献

{"title":"Exosomes in Disease Therapy: Plant-Derived Exosome-Like Nanoparticles Current Status, Challenges, and Future Prospects.","authors":"YuYing Song, NaNa Feng, QingYa Yu, YuanYuan Li, MingKun Meng, Xing Yang, ZhiQiang Gan, Tong Xu, Ce Tang, Yi Zhang","doi":"10.2147/IJN.S540094","DOIUrl":"10.2147/IJN.S540094","url":null,"abstract":"<p><p>Exosomes are nano-sized extracellular vesicles secreted by diverse cell types that mediate intercellular communication through the transfer of proteins, lipids, and nucleic acids. Their ability to cross biological barriers and carry bioactive cargo has led to increasing interest in their use as targeted delivery systems for drugs, genes, and immunomodulatory molecules. Recently, plant-derived exosome-like nanoparticles, PLNs obtained from edible plants and medicinal herbs have emerged as a novel, biocompatible alternative to mammalian exosomes. PLNs exhibit low immunogenicity, enhanced safety, and scalable production, making them ideal candidates for clinical translation. This review synthesizes a wide body of experimental data on the biogenesis, molecular composition, and biological activity of PLNs, and provides a comparative assessment of their therapeutic applications across oncology, immunotherapy, regenerative medicine, and gene therapy. Technological advances in PLN engineering, isolation, and manufacturing are discussed, along with key translational barriers such as stability, regulatory standards, and delivery specificity. This review also discusses the scientific implications of PLNs in advancing precision medicine and propose future directions for their integration into next-generation nanotherapeutics.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10613-10644"},"PeriodicalIF":6.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015143","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":"Preparation Methods of Hydrogel Microspheres and Recent Advances in Their Application for Treating Diabetic Wounds.","authors":"Xian Hu, Min-Xia Zhang, Fa-Wei Xu, Qing-Qing Fang, Jia-Qin Cai, Yi-Qing Chen, Jing-Jing Ma, Wei-Qiang Tan, Yong Wang","doi":"10.2147/IJN.S527650","DOIUrl":"10.2147/IJN.S527650","url":null,"abstract":"<p><p>Diabetic wounds are characterized by complex pathologies, such as vascular changes, nerve damage, and immune dysfunction, which make healing difficult. Hydrogel microspheres have shown great potential in the field of wound treatment due to their excellent biocompatibility, high water content, and soft physical properties. The review summarizes the preparation methods of hydrogel microspheres in detail, including microfluidic technology, spray method, electro spraying, emulsion method, phase separation, photomask method, and 3D printing technology. These methods have significant advantages in particle size control, morphological consistency, and functionalization. It then reviews the applications of hydrogel microspheres in the treatment of diabetic wounds, including the promotion of cell proliferation, migration, angiogenesis, and macrophage polarization, as well as precise treatment through controllable drug release and environmental responsiveness. In addition, the review explores the unique advantages of hydrogel microspheres in dealing with diabetic wounds complicated by infection and reviews the current challenges faced by these technologies in practical applications, such as preparation complexity, cost issues, and prospects for translation. Finally, the review looks forward to the future enhancement of hydrogel microsphere performance and application breadth through interdisciplinary research and new material development, providing more comprehensive and efficient solutions for the treatment of diabetic wounds.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10645-10666"},"PeriodicalIF":6.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000511","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":"The Trilogy of Skin Regeneration via Metal-Organic Frameworks Nanomedicine: Precision Management of Refractory Wounds, Pathological Scarring, and Hair Follicle Reactivation.","authors":"Xiong Lv, Chun Xiang, Yan Zheng, Xu-Ling Lv, Wan-Xuan Zhou","doi":"10.2147/IJN.S548746","DOIUrl":"10.2147/IJN.S548746","url":null,"abstract":"<p><p>Diabetic infected wounds represent a formidable clinical challenge characterized by persistent hyperglycemia-induced pathological cascades that disrupt normal healing processes through multiple mechanisms including chronic inflammation, oxidative stress, and microvascular dysfunction. As prototypical chronic wounds, they exhibit severely impaired tissue regeneration due to this multifaceted dysfunction in both skin architecture and biological function. Metal-organic frameworks (MOFs) have emerged as promising next-generation therapeutic platforms owing to their exceptional structural tunability, multifunctional properties, and precise spatiotemporal drug delivery capabilities. This review examines several critical aspects: (1) fundamental MOF classifications and advanced synthesis methodologies; (2) metal-specific (Zn²⁺, Cu²⁺, Ag⁺, etc.) therapeutic mechanisms against diabetic wound infections; (3) extended applications in pathological scar modulation and hair follicle regeneration through targeted molecular pathway regulation; and (4) the integrated \"healing-scar suppression-functional restoration\" treatment paradigm. We further elucidate critical unresolved challenges in MOF-based skin regeneration, including long-term biosafety and large-scale production issues while providing a comprehensive theoretical framework for future translational research. By uniting prior MOF studies on scar and hair regeneration with pro-healing paradigms, this discussion frames design principles for concurrent structural and functional repair, guiding MOF research from healing to regeneration.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10433-10468"},"PeriodicalIF":6.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015126","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":"Iron Oxide Nanoparticle Uptake, Toxicity, and Steroidogenesis in Adrenocortical Carcinoma Cells Using a Multicellular in vitro Model.","authors":"Ritihaas Surya Challapalli, Cong Hong, Anna Sorushanova, Obdulia Covarrubias-Zambrano, Nathan Mullen, Sarah Feely, Jose Covarrubias, Sunita N Varghese, Constanze Hantel, Peter Owens, Martin O'Halloran, Punit Prakash, Stefan H Bossmann, Michael Conall Dennedy","doi":"10.2147/IJN.S519937","DOIUrl":"10.2147/IJN.S519937","url":null,"abstract":"<p><strong>Introduction: </strong>Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis, limited treatment options, and high recurrence rates. Surgery and mitotane-based chemotherapy remain the standard of care, and new treatment strategies are needed. Iron oxide nanoparticles (IONPs) offer promise as theranostic agents due to their modifiability for selective uptake and imaging.</p><p><strong>Methods: </strong>We investigated the uptake, toxicity, and impact on steroidogenesis of dopamine-coated Fe/Fe₃O₄ core-shell IONPs in three ACC cell lines (H295R, HAC-15, and MUC-1). Uptake was assessed using flow cytometry, confocal microscopy, and TEM. A multicellular transwell model including human endothelial cells (HUVEC) and primary monocytes was used to simulate physiological barriers to delivery.</p><p><strong>Results: </strong>IONP uptake by ACC cells was concentration- and time-dependent, with optimal uptake at 10 µg/mL. Nanoparticles localised primarily to the cytoplasm and vesicular compartments. At this concentration, IONPs did not impair ACC cell viability, proliferation, metabolic activity, or forskolin/angiotensin II-stimulated steroidogenesis. Higher concentrations (≥20 µg/mL) led to aggregation and reduced viability in some cell lines. In the transwell model, primary monocytes and endothelial cells also avidly absorbed IONPs, reducing nanoparticle availability to ACC cells.</p><p><strong>Conclusion: </strong>ACC cells actively internalise IONPs without significant impairment of viability or steroidogenesis at pharmacologically relevant concentrations. However, non-specific uptake by monocytes and endothelial cells reduces delivery efficiency. These findings highlight the need for strategies to enhance tumour-specific targeting and improve biodistribution in future theranostic applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10487-10502"},"PeriodicalIF":6.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992409","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":"Recent Advancement in MRI-Based Nanotheranostic Agents for Tumor Diagnosis and Therapy Integration.","authors":"Li Zhu, Yu Jiang, Haijun Tian, Yongle Yu, Ye Gan, Hong Li, Mingqing Yuan, Xialing Huang, Xu Liu","doi":"10.2147/IJN.S529003","DOIUrl":"10.2147/IJN.S529003","url":null,"abstract":"<p><p>Cancer remains one of the leading causes of mortality worldwide. Although conventional treatment strategies such as chemotherapy, radiotherapy, and surgery have demonstrated therapeutic potential, their clinical effectiveness is often limited by poor targeting specificity, systemic toxicity, and inadequate treatment monitoring. Magnetic resonance imaging (MRI) has emerged as a powerful diagnostic modality owing to its non-invasive nature, high spatial resolution, deep tissue penetration, and real-time imaging capabilities, making it particularly suitable for guiding and evaluating cancer therapies. Recent advances have led to the development of MRI-based nanotheranostic platforms that integrate diagnostic and therapeutic functions within a single system, enabling precise tumor imaging alongside targeted treatment. This review presents a comprehensive overview of recent progress in MRI-guided nanotheranostic agents for cancer diagnosis and therapy, with a focus on their structural design, functional mechanisms, and biomedical applications in both single treatment approaches such as photothermal therapy, photodynamic therapy, chemodynamic therapy, immunotherapy, and ferroptosis, as well as combined therapeutic strategies. In addition, the contribution of MRI to improving treatment precision through image-guided delivery, real-time therapeutic monitoring, and stimulus-responsive activation is discussed. Key challenges including biosafety, design complexity, and barriers to clinical translation are also examined, along with perspectives on future directions for developing intelligent and clinically viable MRI-integrated therapeutic systems.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10503-10540"},"PeriodicalIF":6.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992395","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":"Transplanted Iron Oxide Nanoparticle-Labeled Mesenchymal Stem Cells Exhibit ex vivo Neuronal Firing Activity in Ischemic Stroke Rats.","authors":"Dong-Ming Huang, Chen-Wen Lu, Jong-Kai Hsiao","doi":"10.2147/IJN.S518933","DOIUrl":"10.2147/IJN.S518933","url":null,"abstract":"<p><strong>Purpose: </strong>Mesenchymal stem cell (MSC) therapy shows promise in preclinical ischemic stroke models, yet clinical translation remains inconsistent. To address this gap, we investigated whether labeling MSCs with Ferucarbotran enables magnetic resonance imaging (MRI) tracking and enhances neural differentiation and functional integration, particularly focusing on the novel observation of spontaneous neuronal firing activity in transplanted cells.</p><p><strong>Methods: </strong>Rat MSCs (rMSCs) were transduced with red fluorescent protein (RFP) and labeled with Ferucarbotran to generate Fer-RFP⁺ rMSCs. These were transplanted into rats subjected to middle cerebral artery occlusion. MRI tracked cell migration and localization. Behavioral recovery was evaluated via the corner test, modified neurological severity score (mNSS), and infarct volume analysis. Post-transplantation, Fer-RFP⁺ rMSCs were magnetically isolated for ex vivo electrophysiological and immunocytochemical analyses.</p><p><strong>Results: </strong>Ferucarbotran labeling did not impair rMSC viability and enhanced in vitro proliferation. MRI effectively visualized Fer-RFP⁺ rMSC migration to ischemic regions. Rats receiving Fer-RFP⁺ rMSCs showed significantly improved functional recovery and reduced infarct volumes compared to controls. Remarkably, ex vivo isolated Fer-RFP⁺ rMSCs exhibited spontaneous neuronal firing on multi-electrode array recordings and expressed the neuronal marker NeuN.</p><p><strong>Conclusion: </strong>Ferucarbotran-labeled MSCs not only serve as MRI-visible tracers but also exhibit neuronal electrophysiological properties post-transplantation in an ischemic stroke model. The emergence of spontaneous neuronal firing in ex vivo transplanted MSCs suggests functional neuronal differentiation, potentially underpinning the observed therapeutic effects. These findings offer new mechanistic insights into MSC-mediated stroke recovery and may enhance the translational relevance of MSC-based therapies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10469-10486"},"PeriodicalIF":6.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992466","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":"Exosomes-Based Nanotherapeutic Strategies: An Important Approach for Spinal Cord Injury Repair.","authors":"Cheng Ju, Hui Dong, Renfeng Liu, Xuan Wang, Ruiqing Xu, Huimin Hu, Dingjun Hao","doi":"10.2147/IJN.S539673","DOIUrl":"10.2147/IJN.S539673","url":null,"abstract":"<p><p>The repair and functional regeneration of spinal cord injury (SCI) remains a major challenge and focal point in regenerative medicine. Following SCI significant inflammation and neuronal damage occur. Conventional drug therapies often fail to precisely target the injured areas and cannot cross the blood-spinal cord barrier, severely limiting therapeutic efficacy. Therefore, precision therapeutics are crucial to improve the prognosis of SCI patients. In recent years, exosomes have gained widespread attention as natural delivery vehicles due to their low immunogenicity, high biocompatibility, and efficient delivery capabilities. Exosomes can effectively cross cell membranes and target specific cells, playing an important role in intercellular signaling. This makes them highly promising for precision therapies in SCI. By engineering exosomes for targeted delivery, new strategies can be developed for drug delivery, gene therapy, and personalized treatment after SCI. We aimed to review the biological functions of exosomes derived from different cell sources and discuss the role in tissue repair following SCI. Additionally, we explore the prospects and potential of exosomes in clinical SCI applications, to provide valuable research insights to improve functional recovery and long-term health management for SCI patients in the future.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10407-10431"},"PeriodicalIF":6.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953290","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":"Multifunctional Nanozyme PDA-Cr₂O₃ for the Treatment of Osteoarthritis.","authors":"Can Li, Guiju Chen, Xiongwei Yan, Bingyang Hu, Xiangyun Zhang, Jun Song","doi":"10.2147/IJN.S538289","DOIUrl":"10.2147/IJN.S538289","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is one of the major menaces to human health. Currently, no sufficiently effective medications are available to treat OA clinically. OA is an inflammatory joint disorder. The overproduction of reactive oxygen species (ROS) plays a critical role in initiating and developing OA pathogenesis. ROS scavenging has become a vital target for OA therapy. Although chromium sesquioxide (Cr₂O₃) nanoparticle has been proven to have excellent ROS scavenging ability, its clinical application is limited due to its poor biocompatibility. Polydopamine (PDA) is an excellent carrier with outstanding biocompatibility. PDA-based nanomaterials exhibit significant potential for various ROS-related diseases.</p><p><strong>Methods: </strong>PDA was synthesized through oxidative autopolymerization of dopamine in an alkaline environment. Subsequently, the novel nanozyme PDA-Cr₂O₃ was synthesized by loading Cr₂O₃ onto PDA nanoparticles with the assistance of hydrazine hydrate. Afterward, the cytotoxicity and ROS scavenging capacity of PDA-Cr₂O₃ were examined. Finally, the ability of PDA-Cr₂O₃ to treat OA was explored at both cellular and animal levels.</p><p><strong>Results: </strong>PDA-Cr₂O₃ had low cytotoxicity and toxic side effects in vivo. Moreover, PDA-Cr₂O₃ exhibited a remarkable capacity to scavenge ROS both in cell-free in vitro systems, such as kit-based assays, and in cellular models. It also dramatically decreased the transcriptional level of inflammation-associated genes and the secretion of inflammatory factors of the OA chondrocytes. In animal experiments, PDA-Cr₂O₃ markedly suppressed the progression of OA.</p><p><strong>Conclusion: </strong>PDA-Cr₂O₃ nanozyme had good biocompatibility and could effectively suppress the development of OA by efficiently scavenging ROS, which has important application prospects in OA treatment. This study might offer some new ideas for the treatment of ROS-related diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10369-10387"},"PeriodicalIF":6.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953331","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":"A Hybrid Protein-Oxygen Nanomedicine Overcomes Osimertinib Resistance in NSCLC via HIF-1α/VEGF/EGFR Inhibition.","authors":"Guanming Jiang, Xuyi Liu, Dou Zhang, Zhenying Diao, Xiaojun Yang, Qinquan Tan, Shiyuan Chen, Wan Zhang, Xiumao Yin, Ting Yin, Xiaozhen Wang, Jianping Zhou","doi":"10.2147/IJN.S531571","DOIUrl":"10.2147/IJN.S531571","url":null,"abstract":"<p><strong>Purpose: </strong>Osimertinib, established as the frontline treatment for advanced non-small cell lung cancer (NSCLC), can effectively prolong progression-free survival. However, it faces the problem of reduced treatment persistence due to acquired drug resistance. Meanwhile, tumor hypoxia is also a key driver of drug resistance. This study proposes a hybrid protein oxygen nanocarrier combined with osimertinib and ginsenoside Rg3 to address the drug resistance issue of NSCLC through multiple mechanisms.</p><p><strong>Methods: </strong>A hybrid protein-oxygen multifunctional nanoplatform (OG@HPO) was engineered by co-encapsulating OSI and GRg3 within oxygen-rich protein matrices. Initial confirmed the synthesis of OG@HPO and characterized its drug/oxygen release. Subsequent in vitro assays verified OG@HPO's tumoricidal activity and elucidated its mechanistic. Finally, in vivo evaluations validated the nanoplatform's tumor targeting and anticancer efficacy.</p><p><strong>Results: </strong>Preliminary experiments confirmed successful OG@HPO preparation and validated its drug/oxygen release capacities. In vitro assays demonstrated the potent cytotoxic effects of OG@HPO against H1975 OR cells. In vivo biodistribution studies revealed excellent tumor-targeting of OG@HPO in H1975 OR xenograft mice. Subsequent 18 days therapeutic monitoring showed superior antitumor efficacy accompanied and favorable biosafety profile of OG@HPO. More importantly, in vitro and in vivo studies demonstrated that OG@HPO effectively oxygenate tumor microenvironment, thereby inhibiting hypoxia-driven HIF-1α expression and simultaneously inhibiting the vascular endothelial growth factor (VEGF)/EGFR pathway.</p><p><strong>Conclusion: </strong>OG@HPO represents an innovative multifunctional nanoplatform integrating tumor-targeting, multi-drug delivery, and hypoxia modulation capabilities. By effectively alleviating tumor hypoxia, it achieves multiple inhibition of HIF-1α and EGFR/VEGF pathways. Ultimately, enhances NSCLC sensitivity to osimertinib, thereby reversing acquired resistance. Overall, OG@HPO is regarded as a promising strategy to overcome osimertinib resistance providing a clinically translatable solution.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10389-10405"},"PeriodicalIF":6.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992392","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":"Cardiac Homing Peptide-Functionalized Polymeric Nanoparticles Suppressing SHP1 Alleviate Acute Myocardial Infarction Injury by Promoting Efferocytosis and Inhibiting Inflammation.","authors":"Qi Pan, Guihao Chen, Xiaoli Zhuang, Fei Li, Yuejin Yang","doi":"10.2147/IJN.S533628","DOIUrl":"10.2147/IJN.S533628","url":null,"abstract":"<p><strong>Purpose: </strong>Acute myocardial infarction (AMI) is a major global health concern worldwide. The upregulation of the CD47 on apoptotic cardiomyocytes acts as a \"don't-eat-me\" signal, inhibiting the clearance of apoptotic cells by macrophages (a process known as efferocytosis) via the Signal Regulatory Protein α (SIRPα)/ SH2 Domain-Containing Phosphatase 1 (SHP1) axis, leading to secondary inflammatory activation. Additionally, impairment of this process can result in insufficient macrophage polarization towards the reparative M2 phenotype. Systemic interventions targeting this axis are constrained by potential adverse effects such as promoting fibrosis, suppressing immunity, and interfering with the protective function of the axis to avoid phagocytosis of normal cells.</p><p><strong>Methods: </strong>In this study, a poly(lactic-co-glycolic acid)@Polydopamine (PLGA@PDA) nanoparticle system was developed to deliver the SHP1 inhibitor TPI1 (NP-TPI1). The nanoparticle was modified with cardiac homing peptide (CHP) to enable heart homing (NP-TPI1/P). Raw264.7 cells and mouse AMI models were utilized to assess the pro-efferocytic, anti-inflammatory, and cardioprotective effects of the novel nanosystem.</p><p><strong>Results: </strong>This novel nanoparticle, which is responsive to ROS and low pH, effectively inhibited SHP1 phosphorylation both in vitro and in vivo, thereby restoring timely clearance of apoptotic cells by macrophages. It also promotes M2 polarization and reduces the secondary inflammatory response. These engineered nanoparticles exhibited an enhanced capability to target infarcted lesions, and AMI mice treated with CHP-modified TPI1-loaded nanoparticles showed significantly improved cardiac performance (left ventricular ejection fraction [LVEF] of NP-TPI1/P vs PBS, 49.42±1.88 vs 31.61±2.30 [%] at day 21 post-AMI) and reduced fibrotic area (NP-TPI1/P vs PBS, 11.60±1.60 vs 25.48±1.98 [% of left ventricular]).</p><p><strong>Conclusion: </strong>This study provides new insights into the development of novel, dual-purpose nanomedicines for post-myocardial infarction, and holds significant potential for the clinical translation of efferocytosis in cardiovascular diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10353-10367"},"PeriodicalIF":6.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953183","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}