International Journal of Nanomedicine最新文献

{"title":"Nano-Based Drug Delivery Systems for Managing Diabetes: Recent Advances and Future Prospects.","authors":"Meihan Liu, Rui Wang, Maggie Pui Man Hoi, Yitao Wang, Shengpeng Wang, Ge Li, Chi Teng Vong, Cheong-Meng Chong","doi":"10.2147/IJN.S508875","DOIUrl":"10.2147/IJN.S508875","url":null,"abstract":"<p><p>Diabetes mellitus is a chronic metabolic disorder, which is characterized by high blood glucose levels, and this can lead to serious diabetic complications. According to the World Health Organization, approximately 830 million adults worldwide are living with diabetes in 2024, with its prevalence continuing to rise steadily over the years. To treat this disease, researchers have developed a variety of first-line drugs, such as sulfonylureas and thiazolidinediones. Despite their long clinical use, there are still many drawbacks and limitations. One of the main drawbacks is low bioavailability, this causes the diabetic patients to take the drugs frequently to lower the blood glucose levels continuously. Some patients may have to take multiple drugs to increase the effectiveness of lowering blood glucose levels. To address these limitations, nano-based drug delivery systems have emerged to overcome these problems. It has emerged as a promising approach for diabetes management, which offers controlled and localized release of anti-diabetic drugs, thus enhancing therapeutic efficacy. This review discusses recent advances in the field of nano-based drug delivery systems for diabetes management, safety and toxicity profiles of anti-diabetic drugs, and future perspectives for the development of nanomedicine in diabetic treatment. Literature search was conducted using electronic databases, and only English literatures were used and published between 2014 and 2024. Recent advancements in nanotechnology have facilitated the development of various nanocarriers, such as polymeric carrier nanoparticles, nanoliposomes, nanocrystals, nanosuspension and inorganic nanoparticles, which enhance drug stability, bioavailability, and efficacy. These systems can deliver anti-diabetic drugs and natural compounds more effectively, thereby minimizing side effects and improving patient compliance. As the field continues to evolve, the successful clinical implementation of nanodrugs could revolutionize the management of diabetes and improve the quality of life for millions of diabetic patients worldwide.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6221-6252"},"PeriodicalIF":6.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110678","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":"Ultrasound Molecular Imaging of Blood Vessel Walls and Vulnerable Plaques via CXCR4-Targeted Nanoscale GVs.","authors":"Chen Lin, Xiaoying Li, Yingnan Wu, Yuanyuan Wang, Weijian Song, Fei Yan, Litao Sun","doi":"10.2147/IJN.S504265","DOIUrl":"10.2147/IJN.S504265","url":null,"abstract":"<p><strong>Purpose: </strong>C-X-C chemokine receptor 4 (CXCR4) mediates the inflammatory response of atherosclerotic vulnerable plaques (ASVP) and is a potential biomarker of atherosclerotic vulnerable plaques. The purpose of this study was to use the imaging ability of a new type of ultrasound contrast agent, nanoscale biosynthetic gas vesicles (GVs), on the vascular wall and to combine the specific ligand of CXCR4 to construct a targeted molecular probe to achieve early identification of atherosclerotic vulnerable plaques and guide clinical treatment decisions.</p><p><strong>Materials and methods: </strong>Compared three contrast agents: GVs, the micro-contrast agent SonoVue, and polyethylene glycol (PEG)-modified GVs in the carotid artery. The expression of CXCR4 in atherosclerotic plaques was demonstrated using flow cytometry and immunofluorescence experiments. Cell adhesion and in vivo ultrasound imaging experiments demonstrated their ability to target the nanoscale biosynthetic gas vesicles. The safety of GVs, PEG-GVs, and CXCR4-GVs was tested the CCk8 test, H&E staining, and serum detection.</p><p><strong>Results: </strong>Strong CXCR4 expression was observed in plaques, whereas little expression was observed in normal vessels. GVs can produce stable contrast signals on the carotid artery walls of rats, whereas PEG-GVs can produce more lasting contrast signals on the carotid artery wall of rats. CXCR4-GVs exhibited excellent binding capability to ox-LDL-induced RAW264.7 cells. Animal experiments showed that compared with Con-GVs, CXCR4-GVs injected plaque imaging signal was stronger and more durable. In vitro scanning of vulnerable plaques in rats injected with fluorescent vesicles demonstrated that CXCR4-GVs oozed through the neovasculars within vulnerable plaques and aggregated in vulnerable plaques. Through the CCK8 test, H&E staining, and serum detection, the safety of CXCR4-GVs was confirmed.</p><p><strong>Conclusion: </strong>CXCR4-GVs were constructed as targeted molecular probes, which can be proven to have good targeting properties to vulnerable atherosclerotic plaques.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6205-6220"},"PeriodicalIF":6.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110682","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":"Lung Epithelial Cell Membrane-Camouflaged ROS-Activatable Berberine Nanoparticles for Targeted Treatment in Acute Lung Injury.","authors":"Chengkang Jin, Yingjie Zhang, Lin Chen, Bingqing Chen, Changjiang Chen, Hairui Zhang, Junping Guo, Wei Chen, Yi Shi, Chengping Wen","doi":"10.2147/IJN.S514611","DOIUrl":"10.2147/IJN.S514611","url":null,"abstract":"<p><strong>Introduction: </strong>Acute lung injury (ALI) seriously threatens human health and is induced by multiple factors. When ALI occurs, lung lesions affect gas exchange and may trigger respiratory failure. Current clinical treatments are limited, and traditional drug delivery has drawbacks. Berberine, a natural drug with anti-inflammatory effects, has difficulty in effectively exerting its efficacy.</p><p><strong>Methods: </strong>The study designed a nano-micelle. Hydrophobic berberine was encapsulated with diselenide bonds as the linker. Then, lung epithelial cell membranes were extracted to encapsulate and disguise the nano-micelle. These nanoparticles were injected intravenously. Thanks to the cell membrane's specificity, they could bind to lung tissue, achieving targeted lung delivery. In the inflamed area of acute lung injury, the significantly increased reactive oxygen species level was used to break the diselenide bonds, enabling precise berberine release at the lung injury site.</p><p><strong>Results: </strong>The nano-drug (MM-NPs) was successfully prepared, with the encapsulation efficiency of berberine in the micelles reaching 68.2%. In a ROS environment, the nano-micelles could quickly release over 80% of berberine. In inflammatory MLE-12 cells, MM-NPs responded well to ROS, and cellular inflammatory factor levels were significantly improved after treatment. In a lipopolysaccharide (LPS)-induced pneumonia mouse model, MM-NPs achieved lung targeting. Further studies showed that MM-NPs administration significantly alleviated LPS-induced lung injury in mice. Additionally, evaluation indicated MM-NPs had good in-vivo safety with no obvious adverse reactions.</p><p><strong>Conclusion: </strong>This study successfully developed a novel delivery system, MM-NPs, overcoming berberine's low bioavailability problem in treating acute lung injury. The system has excellent physicochemical properties, biocompatibility, and metabolic safety. In vitro and animal experiments verified it can significantly enhance the therapeutic effect, offering new ideas and hopes for acute lung injury treatment. In the future, clinical trials can be advanced, and new lung targeting strategies explored for more therapeutic breakthroughs.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6163-6183"},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101873","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":"Nanoemulsions Based Therapeutic Strategies: Enhancing Targeted Drug Delivery against Breast Cancer Cells.","authors":"Zahra Izadiyan, Thomas J Webster, Pooneh Kia, Katayoon Kalantari, Misni Misran, Elisa Rasouli, Zahra Maghareh Esfahan, Kamyar Shameli","doi":"10.2147/IJN.S488545","DOIUrl":"10.2147/IJN.S488545","url":null,"abstract":"<p><p>Nanoemulsions (NEs), colloidal systems of nanoscale droplets (~100 nm), have emerged as transformative tools in oncology due to their high surface area-to-volume ratio, tunable physicochemical properties, and capacity for targeted drug delivery. While NEs find applications across diverse fields, their urgency in breast cancer therapy stems from critical limitations of conventional treatments, including systemic toxicity, poor bioavailability, and multidrug resistance. Unlike traditional chemotherapeutics, NEs enable precise tumor targeting via passive mechanisms (eg, enhanced permeability and retention effect) and active strategies (eg, ligand-functionalized surfaces), significantly reducing off-target effects. Their ability to encapsulate hydrophobic drugs, improve solubility, and sustain controlled release enhances therapeutic efficacy while overcoming resistance mechanisms prevalent in aggressive breast cancer subtypes, such as triple-negative and HER2-positive tumors. This review comprehensively analyzes NE formulation techniques (eg, ultrasonication, phase inversion temperature, bubble bursting), stability optimization through surfactant dynamics, and predictive modeling of droplet behavior. A focal point is their role in modulating tumor microenvironments, inducing apoptosis, and inhibiting angiogenesis in preclinical breast cancer models. By spotlighting NE-driven advancements in drug accumulation, reduced relapse rates, and adaptable combination therapies, this article underscores their potential to revolutionize oncology. Future research must prioritize clinical translation, scalability, and multifunctional NE designs to address unmet needs in precision breast cancer treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6133-6162"},"PeriodicalIF":6.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093808","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":"Enhanced Sonodynamic Therapy via Au Nanoclusters Deposited on TiO₂ Nanosheets.","authors":"Lei Huang, Lineng Wei, Dan Li, Weiqing Zhang, Lidong Liu","doi":"10.2147/IJN.S516314","DOIUrl":"10.2147/IJN.S516314","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to enhance the efficacy of sonodynamic therapy (SDT) for breast cancer by engineering TiO₂ nanosheets modified with Au nanoclusters (TiO₂-Au), thereby improving reactive oxygen species (ROS) generation under ultrasound (US) irradiation.</p><p><strong>Methods: </strong>TiO₂-Au sonosensitizers were synthesized via a deposition-precipitation with urea (DPU) method and characterized by TEM, XRD, and XPS. ROS generation efficiency was quantified using DPBF, TMB, and NBT probes, along with electron spin resonance (ESR). In vitro therapeutic performance was assessed in 4T1 breast cancer cells via flow cytometry, Calcein-AM/PI staining, and cell counting kit-8 (CCK-8) assay. In vivo efficacy and biosafety were validated in 4T1 tumor-bearing BALB/c mice through tumor growth monitoring, histological analysis, blood biochemistry, and hemolysis assays.</p><p><strong>Results: </strong>TiO₂-Au_10.5 exhibited enhanced electron-hole separation, reduced bandgap (from 3.2 to 2.8 eV), and significantly boosted ROS generation under US irradiation. In vitro, TiO₂-Au_10.5 combined with US induced a 4.25-fold increase in intracellular ROS and a 4.7-fold higher apoptosis rate compared to TiO₂ + US. In vivo, TiO₂-Au_10.5 + US achieved a tumor growth inhibition index of 76.9% without significant toxicity, as evidenced by normal blood markers, no hemolysis, and no damage to major organs.</p><p><strong>Conclusion: </strong>Au nanocluster modification effectively tunes the sonodynamic performance of TiO₂ nanosheets by modulating electron-hole separation and ROS production. Notably, varying the Au content enabled precise regulation of SDT efficacy, with TiO₂-Au_10.5 achieving optimal therapeutic outcomes. These findings highlight TiO₂-Au as a safe, potent, and composition-tunable sonosensitizer platform for precise and effective cancer therapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6121-6131"},"PeriodicalIF":6.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093802","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":"Mitochondrial Reactive Oxygen Species (mROS) Generation and Cancer: <i>Emerging Nanoparticle Therapeutic Approaches</i>.","authors":"Xinyao Wang, Xiangyang Xiong","doi":"10.2147/IJN.S510972","DOIUrl":"10.2147/IJN.S510972","url":null,"abstract":"<p><p>Mitochondrial reactive oxygen species (mROS) are generated as byproducts of mitochondrial oxidative phosphorylation. Changes in mROS levels are involved in tumorigenesis through their effects on cancer genome instability, sustained cancer cell survival, metabolic reprogramming, and tumor metastasis. Recent advances in nanotechnology offer a promising approach for precise regulation of mROS by either enhancing or depleting mROS generation. This review examines the association between dysregulated mROS levels and key cancer hallmarks. We also discuss the potential applications of mROS-targeted nanoparticles that artificially manipulate ROS levels in the mitochondria to achieve precise delivery of antitumor drugs.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6085-6119"},"PeriodicalIF":6.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093807","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":"Dopamine and Mn(II) Chelate Covalent-Doping Coated Ti(IV)-Nanotheranostics for Magnetic Resonance Imaging Guided Phototherapy in Oral Cancer.","authors":"Zhenghui Li, Xufei Bian, Huiyu Wu, Ling He, Zuhua Zeng, Lei Zhong, Yao Liu, Yu Li, Guihao Hu, Fanglin Mi, Zhen Liu, Jiang Zhu","doi":"10.2147/IJN.S512565","DOIUrl":"10.2147/IJN.S512565","url":null,"abstract":"<p><strong>Purpose: </strong>Phototherapy have gained significant traction in the treatment of tumors. However, the successful implementation of these therapies relies on photosensitizers with superior properties and precise guidance mechanisms.</p><p><strong>Methods: </strong>In this study, we introduce an innovative method for the surface modification of titanium dioxide (TiO₂) nanoparticles through HRP-catalyzed covalent incorporation of Mn(II) chelate (Mn-Dopa) and dopamine.</p><p><strong>Results: </strong>This modification extends TiO₂ nanoparticels' light absorption from ultraviolet to the near-infrared (NIR) range, endowing the nanoparticles with MRI-guided phototherapy capabilities. The resulting nanotheranostics system, TiO₂@PDA-MnDopa, demonstrated over 5-fold enhanced relaxivity compared to the monomeric MnDopa and exhibited synergistic phototherapy effects upon 808 nm laser excitation, with a photothermal conversion efficiency of 15.91%. In vitro and in vivo pharmacodynamics studies showed that the TiO₂@PDA-MnDopa demonstrated good safety in the HSC3 cell line and corresponding tumor-bearing mice, while effectively inhibiting tumor growth under 808 nm laser excitation.</p><p><strong>Conclusion: </strong>This multifunctional nanotheranostic, integrating high relaxivity with synergistic PTT/PDT for MR imaging-guided phototherapy, holds great potential for applications in the early diagnosis, noninvasive treatment, and prognostic evaluation of oral squamous cell carcinoma.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6043-6057"},"PeriodicalIF":6.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093859","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":"Advancements in Cell Membrane-Derived Biomimetic Nanotherapeutics for Breast Cancer.","authors":"Mingtang Zeng, Chenji Hu, Tao Chen, Tingrui Zhao, Xinhua Dai","doi":"10.2147/IJN.S502144","DOIUrl":"10.2147/IJN.S502144","url":null,"abstract":"<p><p>Breast cancer remains the leading cause of female mortality worldwide, necessitating innovative and multifaceted approaches to address its various subtypes. Nanotechnology has attracted considerable attention due to its nanoscale dimensions, diverse carrier types, suitability for hydrophobic drug delivery, and capacity for controlled and targeted administration. Nano-sized particles have become prevalent carriers for therapeutic agents targeting breast cancer, thanks to their reproducible synthesis and adjustable properties, including size, shape, and surface characteristics. In addition, certain nanoparticles can enhance therapeutic effects synergistically. However, the immune system often detects and removes these nanoparticles, limiting their efficacy. As a promising alternative, cell membrane-based delivery systems have gained attention due to their biocompatibility and targeting specificity. These membrane-coated drug delivery systems are derived from various cell sources, including blood cells, cancer cells, and stem cells. Leveraging the unique properties of these cell membranes enables precise targeting of breast cancer tumors and associated biomarkers. Inspired by natural structures, cell membranes disguise nanoparticles in the bloodstream, enhancing their retention time in vivo and improving tumor targeting. Consequently, cell membrane-derived nanoparticles (CMDNPs) have been investigated for their potential applications in breast cancer diagnostics, photothermal therapy (PTT), and vaccine development. This review comprehensively explores the potential and limitations of cell membrane-derived drug delivery systems in clinical applications against breast cancer.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6059-6083"},"PeriodicalIF":6.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093831","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":"Bupivacaine Nanoparticles Inhibit Triple-Negative Breast Tumor Growth by Suppressing the Noradrenergic Nerves in Tumor Microenvironment.","authors":"Haixuan Wu, Xiaoyan Huang, Hui Xu, Hongmei Yang, Zhongqi Liu, Fan Liu, Fengtao Ji, Minghui Cao","doi":"10.2147/IJN.S515895","DOIUrl":"10.2147/IJN.S515895","url":null,"abstract":"<p><strong>Background: </strong>Nerves in the tumor microenvironment (TME) promote malignant phenotypes of cancer. Neuron-targeting cancer treatment strategies have garnered significant attention. However, existing pharmacological or surgical methods of denervation can lead to side effects such as pain and respiratory system issues. Targeted delivery of local anesthetics to the TME using nanotechnology to suppress nerves appears to be a promising approach.</p><p><strong>Methods: </strong>NP-BUP, an acid-responsive nanoparticle encapsulating the local anesthetic bupivacaine, was synthetized using a nano-precipitation method. Immunofluorescence staining was employed to identify the primary types of nerves in breast tumors. In vitro, the impact of the neurotransmitter on the recruitment of macrophages by tumor supernatant is assessed using the transwell assay. ELISA assays and intracellular Ca²⁺ measurement experiments were conducted to evaluate the inhibitory effect of NP-BUP on noradrenergic neurons. In vivo, the impact of NP-BUP on noradrenergic neurons, tumor-associated macrophages (TAMs) infiltration, and tumor growth within the TME were assessed.</p><p><strong>Results: </strong>The predominant type of neuron within breast tumor tissues was found to be noradrenergic neuron. Noradrenergic neuronal uptake of NP-BUP at pH 6.5 was 2.4 times higher than at pH 7.4. In vitro, NP-BUP significantly inhibited the release of norepinephrine (NE), a neurotransmitter that promotes macrophage migration, from adrenergic cells. In vivo, tumor tissues from 4T1 tumor-bearing mice treated with NP-BUP showed a significant reduction in NE content and macrophage infiltration, with tumor volume and weight decreasing by approximately 70% compared to the PBS group.</p><p><strong>Conclusion: </strong>Our study provides a TME pH-responsive nanoplatform for targeted suppression of neuronal control within the TME. Our results demonstrate that specifically modulating innervation within the TME can influence the growth of breast cancer.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6023-6041"},"PeriodicalIF":6.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093856","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":"Delivery of miR-26a-5p by Subcutaneous Adipose Tissue-Derived Extracellular Vesicles Alleviates Acute Lung Injury in Mice Through CHUK/NF-κB Pathway.","authors":"Yu Xie, Liuyi Ran, Ciquan Yue, Chenxing Wang, Fengming Chen, Yadong Su, Yin Qin, Qiuhong Zhang, Jie Liu, Ning Du, Li Zhang, Yu Jiang, Gang Liu","doi":"10.2147/IJN.S514623","DOIUrl":"https://doi.org/10.2147/IJN.S514623","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung injury and high mortality rates due to severe inflammation. Adipose tissue, functioning as both an endocrine and immune organ, plays a crucial role in immune regulation by secreting a variety of adipokines. Among these, adipose tissue-derived extracellular vesicles (EVs) have emerged as novel mediators of intercellular communication, capable of delivering bioactive molecules such as microRNAs to target cells. This study aimed to elucidate the immunomodulatory roles and underlying mechanisms of adipose tissue-derived EVs in the pathogenesis of ARDS.</p><p><strong>Methods: </strong>Subcutaneous adipose tissue extracellular vesicles (SAT-EVs) were collected from the mice via ultracentrifugation. C57BL/6 mice were administered SAT-EVs (1×10^9 particles per mouse) via tail vein injection, followed by an intraperitoneal Lipopolysaccharide (LPS) injection three hours later to induce acute respiratory distress syndrome (ARDS). The mice were euthanized after 18 h to evaluate the permeability of the microvessels and level of inflammation in the lungs. For in vitro experiments, RAW 264.7 macrophages were stimulated with LPS, with or without SAT-EVs, as a control, to evaluate the inflammatory response of the macrophages.</p><p><strong>Results: </strong>SAT-EVs treatment enhanced the survival rate of ARDS mice and reduced pulmonary vascular permeability. SAT-EVs were internalized by alveolar macrophages, leading to an attenuation of inflammation, as indicated by decreased levels of TNF-α, IL-1β, iNOS, PTGS2, and CCL2. Notably, SAT-EVs transferred miR-26a-5p to alveolar macrophages, which directly targeted conserved helix-loop-helix ubiquitous kinase (CHUK), a key regulator of the NF-κB pathway. This inhibition resulted in reduced transcription of inflammatory mediators (iNOS, PTGS2, and IL-1β). In vitro, SAT-EVs were internalized by RAW 264.7 macrophages, leading to the suppression of LPS-induced inflammation, as shown by decreased expression of TNF-α, IL-1β, iNOS, PTGS2, and CCL2. These findings suggest that miR-26a-5p plays a crucial role in the anti-inflammatory effects of SAT-EVs by suppressing CHUK and modulating the NF-κB pathway.</p><p><strong>Conclusion: </strong>SAT-EVs significantly attenuated LPS-induced ARDS, potentially through the CHUK/NF-κB pathway mediated by miR-26a-5p, thereby exerting protective effects against inflammatory lung injury. These findings provide mechanistic insights into the role of SAT-EVs in immune modulation and suggest their potential as a therapeutic strategy for ARDS.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"6001-6021"},"PeriodicalIF":6.6,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077998","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}