International Journal of Nanomedicine最新文献

{"title":"Empagliflozin-Pretreated MSC-Derived Exosomes Enhance Angiogenesis and Wound Healing via PTEN/AKT/VEGF Pathway.","authors":"Hao Wang, Zihao Bai, Yan Qiu, Jiaxi Kou, Yanqing Zhu, Qian Tan, Chen Chen, Ran Mo","doi":"10.2147/IJN.S512074","DOIUrl":"https://doi.org/10.2147/IJN.S512074","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wounds are a common and challenging complication of diabetes, characterized by delayed healing and increased risk of infection. Current treatment methods are limited and often ineffective in promoting wound repair. Mesenchymal stem cell (MSC)-derived exosomes have shown promise in regenerative medicine, but enhancing their therapeutic potential remains a key area of research.</p><p><strong>Methods: </strong>In this study, MSCs were pretreated with empagliflozin (EMPA), and exosomes were isolated using ultracentrifugation. The morphology, size, and protein markers of EMPA-Exos were characterized. Their effects on human umbilical vein endothelial cells (HUVECs) were assessed using EdU assays, CCK-8 assays, scratch assays, Transwell assays, and Matrigel tube formation assays. The PTEN/AKT/VEGF signaling pathway was analyzed through Western blotting. In vivo, diabetic mouse wound models were used to evaluate the healing efficacy of EMPA-Exos.</p><p><strong>Results: </strong>EMPA pretreatment enhanced the functional properties of MSC-derived exosomes, significantly improving HUVECs' proliferation, migration, invasion, and angiogenesis compared to non-pretreated exosomes (P < 0.05). Transcriptomic analysis and pathway activation studies revealed that EMPA-Exos promoted angiogenesis through the PTEN/AKT/VEGF signaling pathway. In vivo experiments demonstrated accelerated wound healing and increased vascularization in diabetic mice treated with EMPA-Exos (P < 0.05).</p><p><strong>Conclusion: </strong>EMPA-pretreated MSC-derived exosomes effectively enhance angiogenesis and accelerate diabetic wound healing by activating the PTEN/AKT/VEGF signaling pathway. This strategy offers a promising approach for improving diabetic wound repair and provides a potential new therapeutic avenue in regenerative medicine.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5119-5136"},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018864","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 in Systemic Autoimmune Diseases: Recent Advances in Diagnostic Biomarkers and Therapeutic Applications.","authors":"Xinchen Lv, Wendong Liu, Xue Zhou, Yu Yang, Wangqian Zhao, Linfeng Meng, Fenghuoyi Mu, Zhixiang Zhang, Shaohua Zhu, Shuai Zhang, Ying Wang","doi":"10.2147/IJN.S506221","DOIUrl":"https://doi.org/10.2147/IJN.S506221","url":null,"abstract":"<p><p>Systemic autoimmune diseases (SADs) encompass a spectrum of organ involvement, clinical heterogeneity, and therapeutic challenges meriting significant research. These conditions involve the immune system mistakenly attacking and damaging multiple body tissues and organs, leading to chronic inflammation and damage. Exosomes are nanoscale extracellular vesicles secreted by cells that modulate intercellular communication and immunity. Accumulating evidence indicates that exosomes have multifaceted roles in the pathogenesis of SADs through processes like cellular signaling, immune modulation, antigen presentation, and inflammatory response. The cargo of exosomes, such as proteins, miRNAs, and lipids, are vital determinants of cellular and humoral immunity. This review examines key signaling pathways in four common SADs, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and Sjögren's syndrome, and explores exosome as non-invasive biomarkers for diagnosis, disease monitoring, and therapeutic response prediction. Additionally, the therapeutic potential of mesenchymal stromal cells (MSCs) or various type of mesenchymal stem cells derived exosomes as cell-free immunotherapies for SADs is highlighted. Engineered exosomes, with enhanced targeting, bioavailability, low toxicity, are emerging as promising drug delivery vehicles. However, challenges such as high production costs, technical complexity, and inefficiency, along with the lack of standardized protocols, limit clinical implementation in SADs. A deeper understanding of exosome roles in SADs pathogenesis and innovative immunotherapies may provide valuable theoretical support for the diagnosis and treatment of these challenging conditions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5137-5160"},"PeriodicalIF":6.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011019","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":"Illuminating Hope for Tumors: The Progress of Light-Activated Nanomaterials in Skin Cancer.","authors":"Huaqing Lei, Hengqing Cui, Yu Xia, Fujia Sun, Wenjun Zhang","doi":"10.2147/IJN.S506000","DOIUrl":"https://doi.org/10.2147/IJN.S506000","url":null,"abstract":"<p><p>Skin cancer is a common malignant tumor that poses significant global health and economic burdens. The main clinical types include malignant melanoma and non-melanoma. Complications such as post-surgical recurrence, wound formation, or disfigurement can severely impact the patient's mental well-being. Traditional treatments such as surgery, chemotherapy, radiation therapy, and immunotherapy often face limitations. These challenges not only reduce the effectiveness of treatments but also negatively impact patients' quality of life. Phototherapy, a widely used and long-standing method in dermatology, presents a promising alternative for skin cancer treatment. Light-triggered nanomaterials further enhance the potential of phototherapy by offering advantages such as improved therapeutic precision, controlled drug release, minimal invasiveness, and reduced damage to surrounding healthy tissues. This review summarizes the application of light-triggered nanomaterials in skin cancer treatment, focusing on the principles, advantages, and design strategies of photodynamic therapy (PDT), photothermal therapy (PTT), and photoacoustic therapy (PAT). In this manuscript we have an in-depth discussion on overcoming translational barriers, including strategies to enhance light penetration, mitigate toxicity, reduce production costs, and optimize delivery systems. Additionally, we discuss the challenges associated with their clinical translation, including limited light penetration in deep tissues, potential toxicity, high production costs, and the need for advanced delivery systems.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5081-5118"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022315","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":"Melanin Nanoparticles as a Safe and Effective Iron Chelation Therapy: An ex vivo Assessment of Human Placental Transfer in Pregnant Beta-Thalassemia.","authors":"Nahla Bakhamis, Toluwalase Awoyemi, Manu Vatish, Helen Townley","doi":"10.2147/IJN.S494710","DOIUrl":"https://doi.org/10.2147/IJN.S494710","url":null,"abstract":"<p><strong>Background: </strong>Iron toxicity is a major contributor to adverse pregnancy outcomes in women with transfusion-dependent thalassemia. Currently used iron chelators are not recommended during pregnancy, as they can cross the placenta causing potential risk to the fetus. However, ceasing medication may adversely affect the mother's health in both the short- and long-term.</p><p><strong>Objective: </strong>We previously demonstrated that melanin nanoparticles can effectively chelate iron, and this has been confirmed by others in iron-overloaded mice. This study aims to assess whether these nanoparticles cross the placenta and evaluate their biocompatibility and haemocompatibility.</p><p><strong>Study design: </strong>A library of 50 nm, 200 nm, and 500 nm melanin nanoparticles were synthesized and coated with Polyethylene Glycol (PEG) to improve their stability. The particles were tested for chelating iron efficacy in and biocompatibility. An in vitro BeWo (choriocarcinoma) cell model and ex vivo human placental perfusion system were used to assess nanoparticle transplacental passage.</p><p><strong>Results: </strong>Melanin nanoparticles of all sizes were able to chelate iron with a maximum adsorption of 14 mm iron/g of material; significantly higher than Desferrioxamine (DFO) of the same concentration. It was also determined that PEGylated melanin nanoparticles with appropriate size (cut off 200 nm) could be restricted from passing across the placental barrier in an in vitro model using a human choriocarcinoma cell line and in an ex vivo human placental perfusion model. The particles did not cause red cell haemolysis or blood clotting at concentrations up to 1 mM.</p><p><strong>Conclusion: </strong>It was demonstrated herein that transport of MNPs across the placental barrier is highly dependent on particle size (cut off size of 200 nm PEGylated MNPs). Findings suggest the possibility of providing a safe method of iron chelation during pregnancy. Future work using in vivo models will be applied to study systemic particle interactions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4983-4999"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017504","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":"Heme Oxygenase-1 Modulates Macrophage Polarization Through Endothelial Exosomal miR-184-3p and Reduces Sepsis-Induce Lung Injury.","authors":"Wei Chen, Yuan Zhang, Jinkun Chen, Shuan Dong, Xiaoyang Wu, Ya Wu, Zhuo Du, Yibo Yang, Lirong Gong, Jianbo Yu","doi":"10.2147/IJN.S506830","DOIUrl":"https://doi.org/10.2147/IJN.S506830","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary microvascular endothelial cells (PMVECs) are notably implicated in the pathogenesis of sepsis-induced lung injury. Exosomes derived from PMVECs facilitate intercellular communication among various cell types, especially crosstalk with macrophages. Heme oxygenase-1 (HO-1), an early stress-responsive enzyme with inherent protective functions, has been implicated in acute lung injury (ALI) mitigation. But research on the mechanism of HO-1 in macrophage polarization via PMVEC exosomes in sepsis-induced lung injury is lacking.</p><p><strong>Methods: </strong>To investigate the role of HO-1 in the interaction between endothelial cells and macrophages, HO-1 knockout mouse model were established. Exosomes from PMVECs were isolated, and differential expression of microRNA (miRNA) was determined by sequencing. An in vitro co-culture system involving Murine Alveolar Macrophage Cell Line (MH-S cells) and HO-1/ PMVECs-derived exosomes (HP-exos) was used to investigate the underlying mechanisms. To further verify the involvement of HO-1 in intercellular communication through exosomal miRNA in vivo, the level of pulmonary inflammation was evaluated, and the polarization of pulmonary macrophages was analyzed.</p><p><strong>Results: </strong>The results showed that miR-184-3p was significantly downregulated in HP-exos, and supplementation of miR-184-3p enhanced the polarization of M1 macrophages, thus intensifying lung inflammation. HO-1 regulates the polarization of macrophages by regulating endothelial exosomes. Overexpression of HO-1 downregulates miR-184-3p, which negatively regulates Semaphorin 7A (Sema7a), which attenuated M1 type macrophages (M1) polarization and augmented M2 type macrophages (M2) polarization, thereby partially mitigating lung injury and inflammation.</p><p><strong>Conclusion: </strong>Collectively, we elucidated a novel potential therapeutic mechanism that HO-1 alleviate inflammation by modulating the M1/M2 ratio in sepsis-induced ALI by regulating miR-184-3p/Sema7a expression.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5039-5057"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006394","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":"Liver-Targeting Nanoparticles GA-MSe@AR Treat NAFLD Through Dual Lipid-Lowering and Antioxidant Efficacy.","authors":"Sheng Lei, Qiang Wu, Bin Zhang, Minqiang Lu, Yu Xia, Ning Li","doi":"10.2147/IJN.S510577","DOIUrl":"https://doi.org/10.2147/IJN.S510577","url":null,"abstract":"<p><strong>Background and purpose: </strong>Non-alcoholic fatty liver disease (NAFLD) is prevalent worldwide and lacks effective treatments. Arctiin (AR), a natural product, has shown promise for NAFLD therapy, due to its antioxidant, anti-inflammatory, and inhibition adipogenesis properties. However, its therapeutic efficacy is hindered by low water solubility, poor bioavailability, and inadequate liver targeting. In this study, selenium-based antioxidant nanoparticles were developed to load and deliver AR to the liver for synergistic AR and selenium effective treatment of NAFLD.</p><p><strong>Methods: </strong>The therapeutic potential of AR was analyzed by network pharmacology. GA-MSe@AR was synthesized by encapsulating AR within galactose-modified mesoporous selenium nanoparticles (GA-MSe) for liver-specific targeting. The nanoparticle size, chemical structure, and elemental composition were explored. The toxicity, cellular uptake, lysosomal escape, and AR release efficiency of GA-MSe@AR were investigated by in vitro experiments. The liver targeting ability of GA-MSe@AR was evaluated through live imaging. The lipid-lowering and antioxidant activities of GA-MSe@AR were assessed in both in vitro and in vivo NAFLD models. Additionally, its effects on inflammation and pancreatic function were analyzed in vivo.</p><p><strong>Results: </strong>Network pharmacology analysis revealed AR may against NAFLD through regulating metabolism, inflammation, and oxidative stress. GA-MSe@AR exhibited low toxicity, efficient cellular uptake, remarkable lysosomal escape ability, and high AR release efficiency in vitro. In both in vitro and in vivo NAFLD models, GA-MSe@AR demonstrated more pronounced lipid-lowering and antioxidant properties than AR and GA-MSe. Additionally, GA-MSe@AR effectively targeted the liver, resulting in a greater decrease in blood glucose, lipids, ALT, AST levels, and reduction liver inflammation, as well as improved pancreatic function in high-fat diet (HFD)-fed mice compared to AR alone.</p><p><strong>Conclusion: </strong>The GA-specific modification enhanced liver-targeted accumulation of the selenium-based nanoparticles, enabling precise targeted delivery of AR. GA-MSe@AR demonstrated superior lipid-lowering efficacy and antioxidant activity in a NAFLD mice model. These findings collectively establish GA-MSe@AR as a promising therapeutic candidate for NAFLD treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5017-5037"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000952","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":"Cutting-Edge Progress in the Acquisition, Modification and Therapeutic Applications of Exosomes for Drug Delivery.","authors":"Yuhao Wang, Shengmeng Yuan, Lihua Zhou, Kexin Yang, Zhaorui Jin, An Lin, Chao Yang, Weidong Tian","doi":"10.2147/IJN.S516840","DOIUrl":"https://doi.org/10.2147/IJN.S516840","url":null,"abstract":"<p><p>Exosomes are vesicles secreted by cells, typically ranging from 30 to 150 nm in diameter, and serve as crucial mediators of intercellular communication. Exosomes are capable of loading various therapeutic substances, such as small molecule compounds, proteins, and oligonucleotides, thereby making them an ideal vehicle for drug delivery. The distinctive biocompatibility, high stability, and targeting properties of exosomes render them highly valuable for future treatments of diseases like cancer and cardiovascular diseases. Despite the potential advantage of exosomes in delivering biologically active molecules, the techniques for the preparation, purification, preservation, and other aspects of stem cell exosomes are not yet mature enough. In this paper, we briefly introduce the composition, biogenesis, and benefits of exosomes, and primarily focus on summarizing the isolation and purification methods of exosomes, the preparation of engineered exosomes, and their clinical applications, to better provide new ideas for the development of exosome drug delivery systems.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5059-5080"},"PeriodicalIF":6.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007363","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":"Exosome-Mediated Mitochondrial Regulation: A Promising Therapeutic Tool for Alzheimer's Disease and Parkinson's Disease.","authors":"Young Hyun Jung, Hyo Youn Jo, Dae Hyun Kim, Yeon Ju Oh, Minsoo Kim, Seunghyun Na, Ho-Yeon Song, Hyun Jik Lee","doi":"10.2147/IJN.S513816","DOIUrl":"https://doi.org/10.2147/IJN.S513816","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and Parkinson's disease (PD) are representative neurodegenerative diseases with abnormal energy metabolism and altered distribution and deformation of mitochondria within neurons, particularly in brain regions such as the hippocampus and substantia nigra. Neurons have high energy demands; thus, maintaining a healthy mitochondrial population is important for their biological function. Recently, exosomes have been reported to have mitochondrial regulatory potential and antineurodegenerative properties. This review presents the mitochondrial abnormalities in brain cells associated with AD and PD and the potential of exosomes to treat these diseases. Specifically, it recapitulates research on the molecular mechanisms whereby exosomes regulate mitochondrial biogenesis, fusion/fission dynamics, mitochondrial transport, and mitophagy. Furthermore, this review discusses exosome-triggered signaling pathways that regulate nuclear factor (erythroid-derived 2)-like 2-dependent mitochondrial antioxidation and hypoxia inducible factor 1α-dependent metabolic reprogramming. In summary, this review aims to provide a profound understanding of the regulatory effect of exosomes on mitochondrial function in neurons and to propose exosome-mediated mitochondrial regulation as a promising strategy for AD and PD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4903-4917"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967849","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":"Synergistic Induction of Immunogenic Cell Death by Biomineralized Manganese and Bisphosphonates Enhances Anti-PD-L1 Therapy in Triple-Negative Breast Cancer.","authors":"Xiuli Zhang, Nan Liu, Mingjing Wei, Chuanlai Yang, Yanhua Lin, Yarong Zeng, Yufang Li, Lizhi Zhou, Tingting Li, Qingbing Zheng, Hai Yu, Jun Zhang, Ying Gu, Ningshao Xia, Shaowei Li","doi":"10.2147/IJN.S502394","DOIUrl":"https://doi.org/10.2147/IJN.S502394","url":null,"abstract":"<p><strong>Background: </strong>Despite therapeutic benefits of anti-Programmed Death-Ligand 1 (PD-L1) therapy in triple-negative breast cancer (TNBC), low response rates and resistance limit its efficacy. Both manganese (Mn) and bisphosphonates (BPs) are known to induce immunogenic cell death (ICD). Strategies to synergistically enhance ICD induction and elucidate the underlying molecular mechanisms remain to be fully explored.</p><p><strong>Methods: </strong>We analyzed the mode of apoptosis and immunogenicity of cancer cells post-treatment using Western blotting, flow cytometry, and confocal microscopy. RNA sequencing was employed to identify activated apoptotic pathways and elucidate the molecular mechanisms underlying ICD when Mn²⁺ and BPs act synergistically. In 4T1 tumor models, we evaluated the synergistic anti-tumor effect of Mn²⁺ and BPs with anti-PD-L1 antibodies.</p><p><strong>Results: </strong>By leveraging the doping capacity of hydroxyapatite (HA) for Mn²⁺ and its high affinity for BPs, we developed MnHARis particles-a biocompatible slow-release system of biomineralized Mn²⁺ and risedronate (Ris). Compared to Mn2+ and Ris alone, MnHARis achieved a synergistic antitumor effect, manifesting as increased cytotoxicity (IC50 reduced by 17 times) and the emergence of more significant mitochondrial autophagic apoptosis (more pronounced nuclear fragmentation, increased ROS levels, significantly decreased ATP levels, depolarization of mitochondrial membrane potential, upregulation of autophagy markers (LC3B and Beclin), and obvious autophagosomes). MnHARis exerts its antitumor effects via the p38-MAPK pathway. Additionally, increased exposure of calreticulin and increased secretion of high mobility group box 1 indicated that MnHARis successfully induced ICD and promoted specific recognition and cross-presentation of damage-associated molecular patterns released by apoptotic tumor cells by activating dendritic cells and pattern recognition receptors, thereby altering TME of TNBC, increasing TILs, and sensitizing TNBC to anti-PD-L1 therapy.</p><p><strong>Conclusion: </strong>MnHARis effectively synergizes Mn²⁺ and Ris to promote autophagic apoptosis and ICD, increasing TILs and sensitizing TNBC to anti-PD-L1 therapy, thus offering a new therapeutic strategy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"5001-5016"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994501","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":"Lymph Node Exosomes Delivery Attenuates Myocardial Ischemia-Reperfusion Injury via Regulating PTEN-PI3K/Akt Pathway Mediated Myocardiocyte Apoptosis.","authors":"Shuaihua Qiao, Baochuan Wu, Lin Chen, Lingyu Ma, Yi Wang, Biao Xu, Rong Gu","doi":"10.2147/IJN.S512135","DOIUrl":"https://doi.org/10.2147/IJN.S512135","url":null,"abstract":"<p><strong>Background: </strong>Ischemia/reperfusion (I/R) injury following acute myocardial infarction (AMI) induces myocardial apoptosis. Exosomes from KLF2-overexpressing endothelial cells (KLF2-EXO) dampened the effects of I/R injury. The intra-lymph node drainage pathway provides an alternative method to study the therapeutic effects of exosomes. In this study, we explored the role of intra-lymph node injection of KLF2-EXO in myocardial I/R injury.</p><p><strong>Method and result: </strong>Exosomes were isolated from KLF2-overexpressing mouse coronary endothelial cell supernatant via gradient centrifugation. The mice were subjected to ischemia and reperfusion, and an appropriate dosage of KLF2-EXO was administrated via intra-inguinal lymph node injection. KLF2-EXO attenuated I/R injury and alleviated myocardiocyte apoptosis in heart tissue, and immunofluorescence staining indicated KLF2-EXO could be transferred into the heart. MiRNA-sequencing of KLF2-EXO implicated that miRNA-486-5p (miR-486-5p) was a potent candidate mediator that inhibited myocardiocyte apoptosis, and the miR-486-5p antagomir reversed the effect. Further bioinformatics analysis and confirmation experiments revealed that PTEN functions as a downstream target and that the PTEN- PI3K/Akt pathway participates in the regulation of cardiomyocyte apoptosis.</p><p><strong>Conclusion: </strong>Our data demonstrated that intra-lymph node injection of KLF2-EXO attenuated myocardial I/R injury in mice by delivering miR-486-5p to target PTEN- PI3K/Akt pathway, which restrained myocardiocyte apoptosis. KLF2-EXO may serve as an alternative therapy for myocardial I/R injury.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4967-4981"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985981","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}