International Journal of Nanomedicine最新文献

{"title":"Recent Advances in Smart Polymers-Based Therapeutics in Ophthalmology.","authors":"Jia'nan Xie, Lili Nie, Ying Pei","doi":"10.2147/IJN.S530124","DOIUrl":"10.2147/IJN.S530124","url":null,"abstract":"<p><p>Ophthalmic diseases represent a significant burden on global health, contributing to widespread visual impairment and blindness. The distinct anatomical and physiological barriers of the eye significantly restrict the use of conventional ocular delivery techniques. This has prompted research into cutting-edge drug delivery methods that optimize therapeutic benefits and reduce adverse effects. The use of polymer-based drug delivery systems is a promising technique that provides regulated drug release over long periods of time, enhances drug stability, and guarantees localized distribution to specific ocular tissues. This field has been revolutionized by recent advancements in smart polymer-based systems, which enable the development of drug delivery platforms that react dynamically to certain stimuli like pH, temperature, light, and enzymes. By releasing the active pharmaceutical ingredients only when specific conditions are met, these stimuli-responsive devices are intended for delivering medications in a controlled manner, improving treatment precision and minimizing undesirable systemic effects. This review summarizes recent developments in smart polymer-based therapies for ophthalmology, highlighting advances in stimuli-responsive, biodegradable, and multifunctional polymers that have the potential to transform ocular drug delivery, enhance therapeutic efficacy, and improve patient adherence in managing various eye conditions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11823-11841"},"PeriodicalIF":6.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199263","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":"Targeting Glucose Transporter 1 (GLUT1) in Cancer: Molecular Mechanisms and Nanomedicine Applications.","authors":"Zhen Ren, Jingyuan Zhao, Shuai Li, Hong Yuan","doi":"10.2147/IJN.S534976","DOIUrl":"10.2147/IJN.S534976","url":null,"abstract":"<p><p>Glucose transporter 1 (GLUT1), a central orchestrator of tumor metabolic reprogramming, sustains malignant progression by enforcing glycolytic dependency and conferring therapeutic resistance. While conventional GLUT1-targeted small-molecule inhibitors demonstrate preclinical efficacy through glucose transport blockade and chemo-radiosensitization, their clinical translation is impeded by intrinsic limitations. Emerging nanomedicine paradigms have redefined GLUT1-targeted interventions through multifunctional platforms that synergistically unify precision therapeutics, imaging guidance, and immunometabolic modulation. Meanwhile, advanced formulations further exploit GLUT1-mediated endocytosis to achieve blood-brain barrier penetration, thus potentially addressing key challenges in the treatment of CNS malignancies. Notably, combinatorial nanoarchitectures simultaneously disrupt metabolic pathways and reprogram immunosuppressive niches via dual-targeting strategies, thereby counteracting tumor adaptation mechanisms. These innovations transcend conventional therapeutic boundaries by establishing metabolic-immune interplay regulation and barrier-defying delivery systems. This review systematically analyses the evolving landscape of GLUT1-targeted nanomedicine, evaluating both traditional molecular inhibitors and next-generation nanoplatforms that harness GLUT1 through diverse modalities. By dissecting molecular mechanisms and translational applications, we elucidate the diagnostic and therapeutic value of GLUT1-targeted nano-strategies in precision oncology while outlining future directions for clinical implementation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11859-11879"},"PeriodicalIF":6.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206501","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-Drug Delivery System Targeting the Oxidative Stress Microenvironment: A Prospective Strategy for Intervertebral Disc Degeneration Treatment.","authors":"Yidian Wang, Pengfei Wen, Bin-Fei Zhang, Shouye Hu, Zhi Yang","doi":"10.2147/IJN.S529127","DOIUrl":"10.2147/IJN.S529127","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is the main cause of low back pain (LBP), which imposes a heavy burden on individuals and society. At present, the treatment methods for IDD aim to control clinical symptoms, and it is difficult to fundamentally reverse IDD and reconstruct its mechanical function. Related studies have shown that oxidative stress is a key factor in promoting intervertebral disc (IVD) degeneration and impeding its repair, so antioxidant therapy may be effective in improving or reversing IDD progression. However, considering the non-targeted systemic cytotoxicity and limited bioavailability of antioxidant biopharmaceuticals, it is urgent to establish an efficient drug delivery system. With the development and innovation of nanomedicine and materials science, nano-drug delivery systems (NDDSs) have shown broad application prospects in various diseases. Relying on the characteristics of nanoscale materials, NDDSs can achieve good biodegradability, biocompatibility, targeted drug delivery, and controlled drug release, thereby enhancing the efficacy of antioxidant preparations. This review not only summarizes the research progress of NDDSs in the treatment of IDD, but also evaluates the advantages and challenges faced by various NDDSs. We anticipate that the perspectives articulated in this review will offer valuable insights for the precise management of IDD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11717-11780"},"PeriodicalIF":6.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199177","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":"Fabrication and Preclinical Evaluation of Hyaluronic Acid/Aminoclay Nanocomposite Microneedles for Noninvasive Delivery of Semaglutide in Anti-Obesity Therapy.","authors":"Chang Rim Woo, Gyu Lin Kim, Hyo-Kyung Han","doi":"10.2147/IJN.S544952","DOIUrl":"10.2147/IJN.S544952","url":null,"abstract":"<p><strong>Introduction: </strong>Injectable formulations are common for protein-based therapeutics. However, non-injectable formulations are crucial for improving patient compliance. This study aims to develop hyaluronic acid/aminoclay-based dissolving microneedles as a noninvasive delivery system for semaglutide in the treatment of obesity.</p><p><strong>Methods: </strong>The core nanocomplex (Sema-AC) was formed by combining semaglutide (Sema) with aminoclay (AC) via electrostatic interaction. This nanocomplex was then mixed with hyaluronic acid (HA) of varying molecular weights and poured into a reverse polydimethylsiloxane (PDMS) mold to create dissolving microneedles (MNs). Various in vitro and in vivo studies were performed to evaluate the physicochemical properties and therapeutic efficacy of the MNs.</p><p><strong>Results: </strong>Among the developed MNs, Sema-AC/HA10 demonstrated a mechanical strength of 0.37 ± 0.020 N/needle and retained stable physicochemical and morphological properties at 25°C during storage. Encapsulated Sema retained its conformational stability within the MNs. Sema-AC/HA10 dissolved rapidly upon skin insertion, enabling efficient transdermal drug absorption. The MNs containing Sema-AC nanocomplex significantly enhanced the systemic drug exposure compared to the MN loaded with the free drug. Consequently, Sema-AC/HA10 demonstrated in vivo efficacy comparable to that of subcutaneous Sema injection in type 2 diabetic rats, significantly reducing blood glucose, HbA1c, total cholesterol, triglycerides, food intake, water consumption, and body weight\".</p><p><strong>Conclusion: </strong>These findings suggest that Sema-AC/HA10 is an effective transdermal delivery system for semaglutide.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11843-11858"},"PeriodicalIF":6.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199204","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":"Exosomal miR-450b-5p Secreted from Exendin-4-Stimulated Endothelial Cells Protects Retinal Ganglion Cells Against Ischemia Reperfusion Injury.","authors":"Yanan Sun, Ruyi Zhai, Qilian Sheng, Yue Ying, Ye Lin Kwan, Xintong Fan, Huan Xu, Xiangmei Kong","doi":"10.2147/IJN.S525339","DOIUrl":"10.2147/IJN.S525339","url":null,"abstract":"<p><strong>Background: </strong>Retinal ischemia-reperfusion (RIR) injury represents a critical pathophysiological mechanism underlying various ocular ischemic diseases, characterized by progressive loss of retinal ganglion cells (RGCs). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor (GLP-1R) agonist drug in the treatment of type 2 diabetes mellitus, has been reported to protect against ischemia-reperfusion (IR) injury in various vital organs. However, the potential neuroprotective effect of Ex-4 under RIR injury has been poorly understood.</p><p><strong>Methods: </strong>Immunofluorescence staining assay, hematoxylin and eosin (HE) staining were conducted to evaluate the neuroprotective role of Ex-4. A co-culture assay of human retinal vascular endothelial cells (HRVECs) and RGCs was established. Extracellular vesicles (EVs) were isolated from the culture supernatant of HRVECs with (E-EVs) or without Ex-4 treatment (O-EVs) under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA) and Nano-flow cytometry (NanoFCM) were used to detect the presence and purity of EVs. Cell activity, reactive oxygen species (ROS) level, and cell death rate of RGCs were evaluated. Further global miRNA sequencing was performed on E-EVs or O-EVs to explore potential mechanisms.</p><p><strong>Results: </strong>Our findings revealed that Ex-4 had a GLP-1R-dependent neuroprotective effect on RGCs. Vascular endothelial cells (VECs) -derived EVs mediate the protective effect of Ex-4 on RGCs under acute RIR injury. We identified miR-450b-5p as a highly enriched miRNA in E-EVs. Treatment with either E-EVs or miR-450b-5p mimics significantly protected RGCs against RIR-induced injury. Mechanistic investigations identified acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) as a direct target of miR-450b-5p.</p><p><strong>Conclusion: </strong>Ex-4 exerts its neuroprotective effects under RIR injury by stimulating retinal VECs to secrete miR-450b-5p-enriched EVs, thereby revealing a novel endothelial-mediated neuroprotective pathway in ischemia diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11881-11894"},"PeriodicalIF":6.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199255","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 Study on Targeted Therapy of Osteosarcoma Using Tripterine Loaded Polydopamine Mesoporous Microspheres Combined with Photothermal Therapy.","authors":"Molin Li, Yufei Ma, Hui Yao, Hao Jia, Yalan Wang, Xuefeng Tang","doi":"10.2147/IJN.S527094","DOIUrl":"10.2147/IJN.S527094","url":null,"abstract":"<p><strong>Purpose: </strong>Osteosarcoma poses significant clinical challenges due to its high recurrence, metastatic potential, and poor prognosis. Celastrol (CLT), known for its antitumor, immunomodulatory, and osteogenic regulatory properties, has garnered substantial interest. Developing a targeted CLT delivery system is critical to enable precise drug release, integrate photothermal therapy, remodel the tumor microenvironment, and improve post-surgical treatment and repair in osteosarcoma.</p><p><strong>Methods: </strong>Using emulsion-induced interface assembly, we synthesized mesoporous polydopamine-polyethylene glycol (MPDA-PEG) nanospheres and loaded them with celastrol to fabricate the targeted system MPDA-PEG-CLT. We characterized the nanospheres' physicochemical properties and evaluated MPDA-PEG-CLT's efficacy in synergistic drug-photothermal therapy for osteosarcoma through in vitro and in vivo experiments.</p><p><strong>Results: </strong>MPDA-PEG-CLT achieved a drug loading capacity of ~14% and a photothermal conversion efficiency of 37.6% under 808 nm NIR irradiation, which enhanced celastrol release. The system induced osteosarcoma cell apoptosis, promoted bone marrow mesenchymal stem cell (BMSC) differentiation, and ameliorated the lesion microenvironment, resulting in efficient tumor ablation in mice.</p><p><strong>Conclusion: </strong>MPDA-PEG-CLT significantly enhances celastrol's targeted delivery efficiency, promotes mitochondrial apoptosis in osteosarcoma cells, synergizes with photothermal therapy to eradicate tumors, and improves the bone tissue microenvironment in lesions. This system offers a promising strategy for post-surgical osteosarcoma treatment and repair.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11803-11821"},"PeriodicalIF":6.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191689","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":"Advancing Spinal Cord Injury Repair: The Role of Conductive Hydrogels in Neurotissue Engineering.","authors":"Haorui Du, Jie Zhao, Jintao Wang, Xiaoyu Yang, Su Pan","doi":"10.2147/IJN.S553136","DOIUrl":"10.2147/IJN.S553136","url":null,"abstract":"<p><p>Spinal Cord Injury (SCI) is a devastating condition of the central nervous system, affecting a significant number of individuals globally. It leads to irreversible motor, sensory, and autonomic dysfunctions, placing a substantial burden on both patients and society. As a result, there is an urgent need for more effective therapeutic strategies. In recent years, the field of neurotissue engineering has made remarkable progress, offering new avenues for spinal cord injury repair. Among these advancements, conductive hydrogels have gained considerable attention due to their ability to mimic the electrical signaling properties of the spinal cord. These hydrogels not only replicate the complex electrical environment of the spinal cord but also enable non-invasive modulation of electrical signals, which can influence neuronal cell behavior. Additionally, conductive hydrogels provide essential mechanical support and serve as carriers for various drugs, bioactive factors, and cells, which can restore the disrupted microenvironment and promote axonal regeneration, remyelination, and functional recovery after SCI. This paper thoroughly investigates the pathophysiological mechanisms underlying SCI, systematically analyzes the different types of conductive materials used in hydrogels, and evaluates their combinations and functions. Furthermore, it discusses the technical challenges, bottlenecks, and future directions for the development of functional biomaterials aimed at effective SCI repair, offering insights for the creation of innovative therapeutic strategies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11781-11802"},"PeriodicalIF":6.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199197","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":"MOF-Mediated Aloe-Emodin Delivery Enhances Hepatocellular Carcinoma Immunotherapy via Pyroptosis and Immunosuppressant Synergy.","authors":"Huaying Xie, Xiaoyuan Yi, Kunzhao Huang, Jianzhang Luo, Qingyu Zeng, Feifei He, Liyan Wang","doi":"10.2147/IJN.S533216","DOIUrl":"10.2147/IJN.S533216","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatocellular carcinoma (HCC) remains a major global oncological burden, with conventional therapies showing limited efficacy. This study aimed to utilize pyroptosis to alleviate the tumor's immunosuppressive microenvironment, enhance systemic immunity, and improve immunotherapy efficacy, focusing on precise selection of pyroptosis inducers, immunotherapeutic agents, and drug delivery strategies.</p><p><strong>Methods: </strong>After synthesizing AE-FeMn/FA, its morphology, particle size, and Zeta potential were characterized. We evaluated its catalytic performance in activating H₂O₂ to produce ·OH, ability to trigger cellular pyroptosis, and in vitro/in vivo anti-tumor effects. Combined with BMS-202, we explored suppression of the PD-1/PD-L1 complex and synergistic induction of pyroptosis.</p><p><strong>Results: </strong>Intravenous AE-FeMn/FA targeted HCC, with controlled AE release triggering pyroptosis and anti-tumor immunity. BMS-202 alleviated immunosuppression, enhancing AE-FeMn/FA-induced anti-tumor responses, achieving synergistic immune-mediated cancer cell elimination.</p><p><strong>Conclusion: </strong>The synergistic approach of pyroptosis combined with an enhanced immunotherapy nanoplatform shows promise as an effective HCC immunotherapy strategy, with significant clinical translation potential. Future studies will optimize the platform and conduct clinical trials.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11647-11667"},"PeriodicalIF":6.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185830","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":"Hepatotoxicity of Nanoparticle-Based Anti-Cancer Drugs: Insights into Toxicity and Mitigation Strategies.","authors":"Marcin Skorzynski, Magdalena Krol, Agata Braniewska","doi":"10.2147/IJN.S543433","DOIUrl":"10.2147/IJN.S543433","url":null,"abstract":"<p><p>Despite significant progress in developing novel, efficient nanoparticle-based anticancer drugs, hepatotoxicity remains a major challenge. The liver, as the primary organ responsible for detoxification, is particularly susceptible to nanoparticle accumulation, particularly through the action of Browicz-Kupffer cells (B-KCs) and liver sinusoidal endothelial cells (LSECs). These phagocytic cells accumulate nanoparticles, leading to the production of reactive oxygen species (ROS), interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), which ultimately cause hepatocyte damage. In recent years, various nanoparticle modification strategies have been investigated to reduce hepatotoxicity. One of the most common and effective approaches is the PEGylation of liposomes and graphene nanoparticles, which decreases their uptake by the liver via the reticuloendothelial system (RES). Other strategies to mitigate hepatotoxicity are also being explored, including the incorporation of negatively charged lipids into liposomes, charge manipulation of inorganic-organic nanoparticles, the use of specific protein-based nanoparticles that selectively bind to cancer cells (thereby reducing hepatic uptake), the use of appropriate viral capsids in the production of virus-like protein-based drugs, and the manipulation of the size of protein, metal and graphene nanoparticles. Moreover, modifications aimed at pH-responsive drug release are employed in liposomes, self-assembled and graphene nanoparticles. This article discusses several types of nanoparticles used as carriers in currently approved therapies and explores potential strategies to minimize their hepatotoxicity.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11697-11715"},"PeriodicalIF":6.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185835","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":"Intratracheal Instillation of Silver Nanoparticles to Rats Induces Mitochondrial Fission and Aortic Damage: Protective Effect of Sodium Selenite.","authors":"Shan He, P Andy Li, Jing He, Zhizhong Wang, Xuexing Liang, Zhehao He, Shaobin Jia, Wanrui Ma","doi":"10.2147/IJN.S524020","DOIUrl":"10.2147/IJN.S524020","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the influence of AgNPs intratracheal instillation on mitochondrial fission in aortic endothelial cells of rats and to explore the therapeutic effects of sodium selenite (Se).</p><p><strong>Animals and methods: </strong>Male Sprague Dawley rats were divided into four groups (n=8): Control group (A), AgNPs exposure group (B), Se treated group (C), and Se+ AgNPs treated group (D). Rats in groups B and D received one dose of intratracheal instillation of AgNPs, while groups A and C received the same volume of 0.9% NaCl intratracheally. Rats in groups C and D were also intraperitoneally injected with sodium selenite for 7 days immediately after the AgNPs exposure. Morphological changes of the aorta were assessed using hematoxylin and eosin (HE) staining and electron microscopy. Masson's Trichrome Staining assayed collagen deposition in the aorta. Reactive oxygen species (ROS) generation, caspase-3 activity, and mitochondrial fission markers were analyzed.</p><p><strong>Results: </strong>Exposure to AgNPs increased collagen deposition and caused ultrastructural damage to endothelial cells in the aorta, including reduction of cytosolic contents, dissolution of mitochondrial cristae, and swollen mitochondria. Levels of ROS and cleaved caspase-3 increased moderately in AgNPs group (p<0.05 vs Control). Mitochondrial fission markers Dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) in the aortic tissue homogenate of the AgNPs group nearly doubled the values of those in Control group (p<0.05 vs Control). Se alleviated AgNPs-induced ultrastructure changes and this effect was associated with suppressed ROS accumulation, inhibited caspase-3 activation, and attenuated mitochondrial fission.</p><p><strong>Conclusion: </strong>This study demonstrates that AgNPs induced oxidative stress, caspase 3 activation, and mitochondrial fission are linked to the morphological alterations of the aortic endothelial cells; and these adverse effects resulted from AgNPs can be alleviated by sodium selenite, suggesting that selenite could be used as a protective agent against AgNPs toxicity.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"11685-11696"},"PeriodicalIF":6.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185822","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}