Journal of Nanobiotechnology最新文献

{"title":"Advanced integrated SERS-based strategies for the early diagnosis of upper gastrointestinal cancers.","authors":"Qian Wang, Siyi Jiang, Shuyu Zhai, Wenjia Yin, Yao Sun, Huifang Zhao, Ruiping Zhang","doi":"10.1186/s12951-026-04844-x","DOIUrl":"10.1186/s12951-026-04844-x","url":null,"abstract":"<p><p>Upper gastrointestinal (UGI) cancers are associated with high incidence and poor prognosis due to their insidious onset, posing a serious threat to human health. Traditional diagnostic approaches, including endoscopic biopsy, imaging modalities, and molecular assays, frequently suffer from tedious procedures and insufficient sensitivity. Therefore, it is imperative to develop novel technologies for the early diagnosis of UGI cancers to reduce diagnostic delay, ensure diagnostic accuracy, and ultimately improve patient survival rates. Owing to its exceptional sensitivity and rich molecular fingerprinting information, surface-enhanced Raman spectroscopy (SERS) has emerged as an invaluable analytical tool for uncovering metabolic molecular alterations, thereby facilitating rapid, sensitive, and early-stage diagnosis of UGI cancers. Herein, this review not only outlines the principles and detection strategies of SERS technology, but also highlights its recent advances in the early diagnosis of UGI cancers, particularly in conjunction with other innovative technologies. Ultimately, the current challenges and future development directions are discussed, providing a valuable perspective to guide future efforts toward early UGI cancer screening.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing chitosan-based biomaterials for advanced cancer immunotherapy: from nanocarriers to tumor microenvironment modulation.","authors":"Yun Wang, Yan Fan, Jing Zhang, Ning Sun, Kang Chen, Qasim Khan, Haishan Zhang","doi":"10.1186/s12951-026-04821-4","DOIUrl":"10.1186/s12951-026-04821-4","url":null,"abstract":"<p><p>Cancer immunotherapy has transformed oncology, however, its clinical efficacy remains limited by immunosuppressive tumor microenvironments (TMEs), poor therapeutic delivery, systematic toxicity, treatment resistance. Chitosan, a biocompatible and biodegradable polysaccharide, has emerged as a versatile biomaterial capable of addressing these challenges through both intrinsics immunomodulatory activity and advanced drug-delivery functions. This review summarizs recent advances in chitosan-based biomaterials for cancer immunotherapy, highlighting their ability to activate innate and adaptive immune responses through pathways involving patterns recognition receptors, cyclic GMP-AMP synthase (cGAS)=simulator of interferon genes (STING) signaling, dendric cells (DCs)macrophages, natural killer (NK) cells and T lymphocytes. The design and application of chitosan-based nanoparticles and hydrogels as platformsfor delivering cytokines, nucleic acids, immune adjuvant, cancer vaccines and immune checkpoint therapeutics are discussed. Particular attention is given to their roles in TME remodeling, sustained local drug release, postsurgical immunotherapy, and combination approaches that integrate chemotherapy, radiotherapy (RT), phototherapy and immunotherapy. Emerging strategies, including stimuli-responsive systems, biomimetic formulations, and multifunctional nanoplatforms are also discussed. Finally, we discuss the current translational current translational challenges and future perspectives, emphasizing the potential of chitosan-based biomaterials to enhance antitumor immunity and improve clinical outcomes in cancer immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of ⁶⁸Ga-lactosylated human serum albumin (LSA) for PET-based quantitative evaluation of hepatic functional reserve in liver fibrosis models.","authors":"Boeun Park, Ji Yong Park, Kisoo Pahk, Jin Sil Kim, Chanmin Joung, Jung Woo Byun, Ran Ji Yoo, Ji Seon Mun, Kyungsil Chae, Jae Min Jeong, Sungeun Kim, Jin Chul Paeng, Yun-Sang Lee","doi":"10.1186/s12951-026-04827-y","DOIUrl":"10.1186/s12951-026-04827-y","url":null,"abstract":"<p><p>Accurate preoperative assessment of hepatic functional reserve (HFR) and future remnant liver function is essential for reducing postoperative morbidity and mortality after liver surgery, yet current clinical methods remain indirect and provide limited spatial and quantitative information. Here, we developed an asialoglycoprotein receptor (ASGPR)-targeted tracer for positron emission tomography (PET), [⁶⁸Ga]Ga-NOTA-lactosylated human serum albumin ([⁶⁸Ga]Ga-NOTA-LSA), and systematically optimized the degree of lactosylation for hepatic imaging. Comparative evaluation of lactosylated human serum albumin constructs bearing 7 or 12 lactose moieties [LSA (7) and LSA (12)] identified LSA (12) as the preferred construct with more favorable hepatocyte targeting in vivo. [⁶⁸Ga]Ga-NOTA-LSA was radiolabeled with high efficiency within 10 min at room temperature and showed favorable radiochemical stability in phosphate-buffered saline and serum. The optimized precursor was further formulated as a lyophilized kit, enabling rapid one-step ⁶⁸Ga labeling, reproducible preparation, and storage stability. In thioacetamide-induced rat liver fibrosis models, including untreated, spontaneous recovery, and pirfenidone-treated groups, [⁶⁸Ga]Ga-NOTA-LSA PET/CT enabled single-time-point quantitative assessment of hepatic function, with 60 min post-injection selected as the optimal imaging time point. Hepatic uptake and liver-to-heart ratios were markedly reduced in fibrotic livers and progressively restored in recovery and treatment models. PET-derived parameters correlated with histological fibrosis, ASGPR expression, fibrogenic and apoptotic markers, and serum liver injury biomarkers. In contrast, ^99mTc-mebrofenin required serial imaging to evaluate hepatobiliary kinetics, highlighting mechanistic and workflow differences between transport-based scintigraphy and receptor-associated PET uptake imaging. Reduced hepatic uptake was also reproduced in a fibrotic mouse model. In addition, single-dose toxicity testing showed favorable acute tolerability of non-radioactive NOTA-LSA. Together, these findings support the feasibility of [⁶⁸Ga]Ga-NOTA-LSA as a reproducible and quantitative PET platform for HFR imaging with translational potential.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticles and their significant risks: a comprehensive review of toxicological and regulatory perspectives.","authors":"Beata Skonieczna, Natalia Nazarko, Ewelina Godlewska, Natalia Wasiluk, Ewa Katarzyna Czech, Agnieszka Zofia Wilczewska, Elżbieta Regulska, Halina Car, Katarzyna Niemirowicz-Laskowska","doi":"10.1186/s12951-026-04801-8","DOIUrl":"https://doi.org/10.1186/s12951-026-04801-8","url":null,"abstract":"<p><strong>Background: </strong>Nanoparticles are increasingly important as drug carriers due to their ability to enhance solubility, stability, and selective delivery of therapeutic agents, enabling accumulation at disease sites, interaction with cell-surface receptors, and penetration of biological barriers such as the blood-brain barrier. Despite these numerous advantages, their potential toxicity remains a key obstacle to safe clinical use. Emerging evidence suggests that nanoparticles may alter the composition of the gut microbiome, potentially affecting metabolism, immune homeostasis, neurobehavioral pathways, and reproductive function by influencing hormonal regulation and fertility.</p><p><strong>Aim of the review: </strong>This review provides a detailed analysis of the toxicological aspects of nanoparticles, including cytotoxicity, oxidative stress, potential genotoxicity, and effects on immune responses such as inflammation and immunosuppression. In vivo biodistribution, organ accumulation, and effects on liver enzymes are also discussed, emphasizing the role of the liver in drug metabolism and the potential risk of impaired detoxification. Additionally, the review examines the effects of nanoparticles on the gut microbiome and reproductive system. It emphasizes their capacity to disrupt the microbial balance, the intestinal barrier integrity, and reproductive hormone homeostasis. We discuss regulatory issues for nanotechnology-based medicinal products, emphasizing the importance of standardized testing protocols and long-term safety assessments. Finally, future perspectives and developmental directions for nanoparticles have been highlighted.</p><p><strong>Conclusion: </strong>This review highlights the need for a comprehensive understanding of nanoparticle toxicity mechanisms, which is crucial for their safe design and further development in nano-based therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149268965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-free ferroptosis-like nanoreactors for microenvironment-activated antibiofilm therapy via cascade lipid peroxidation amplification.","authors":"Zhengcai Guo, Zhiling Chen, Yang Li, Ziming Wei, Nan Zhang, Lidi Li, Yi Li, Qionglin Zhou, Lina Niu, Delun Chen, Yang Cao, Jinchun Tu, Rui Zhang, Qiang Wu","doi":"10.1186/s12951-026-04851-y","DOIUrl":"https://doi.org/10.1186/s12951-026-04851-y","url":null,"abstract":"<p><p>Ferroptosis-like nanotherapeutic strategies have emerged as promising approaches for eradicating bacterial biofilms; however, conventional iron-based nanotechnologies are often constrained by limited intracellular iron accumulation, enhanced bacterial antioxidant defenses, and insufficient oxidative substrates under hypoxic infection microenvironments. Herein, we report an iron-free ferroptosis-like antibacterial nanoreactor constructed by integrating vanadium carbide MXene (V₂CT_x), zinc peroxide (ZnO₂), bovine serum albumin (BSA), and indocyanine green (ICG). Under acidic infection conditions, ZnO₂ undergoes sustained decomposition to generate hydrogen peroxide and oxygen, while the multivalent V₂CT_x backbone mediates Fenton-like redox cycling and depletes intracellular glutathione, collectively disrupting bacterial redox homeostasis. Upon near-infrared (NIR) irradiation, ICG produces abundant singlet oxygen (¹O₂) to initiate lipid peroxidation, and the accompanying photothermal effect further accelerates oxidative reaction kinetics within the confined nanoreactor. This cascade-amplified process enhances membrane lipid peroxidation, resulting in ferroptosis-like membrane collapse and irreversible bacterial death. Comprehensive mechanistic investigations, including membrane integrity analysis, radical scavenging assays, and oxidative lipidomics, identify lipid peroxidation as the dominant lethal pathway, characterized by extensive remodeling of arachidonic acid-, linoleic acid-, and omega-3 polyunsaturated fatty acid-derived oxidation products. Notably, the nanoreactor demonstrates potent therapeutic efficacy in infected wounds and abscess biofilm models while simultaneously alleviating inflammation and promoting tissue regeneration. Collectively, this work establishes a controllable and amplifiable iron-free ferroptosis-like antibacterial paradigm, substantially expanding the design scope of ferroptosis-inspired therapies and highlighting nanoreactor engineering as a powerful strategy for precisely regulating oxidative lethality against drug-resistant bacterial biofilm infections.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149268952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel nanotherapeutic strategy targeting mechanical tumor microenvironment in bladder cancer.","authors":"Xu Wang, Long Jin, Qiushuang Zhang, Mingyu Li, Min Wang, Qi Jia, Haitao Fan","doi":"10.1186/s12951-026-04855-8","DOIUrl":"https://doi.org/10.1186/s12951-026-04855-8","url":null,"abstract":"<p><p>This study investigated the mechanistic role of mechanical stress (MS) induced by partial bladder outlet obstruction (pBOO) in promoting bladder cancer (BC) growth and metastasis through single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) techniques. An orthotopic BC mouse model subjected to pBOO was utilized to replicate contractile stress linked to lower urinary tract obstruction, with in vitro models providing supplementary insights into MS effects on BC malignancy. Exploratory scRNA-seq analysis suggested distinct epithelial subpopulations with elevated mechanical stress scores, while RNA-seq highlighted the prominent activation of the YAP/TAZ/AXL signaling axis by MS. Additionally, a CD44-targeted polymer-chitosan-lipid nanoparticle (PCL-NP@VP/siYAP) was developed for the concurrent delivery of Verteporfin and YAP-targeting siRNA to counteract the mechanical tumor microenvironment. The nanoparticles demonstrated favorable particle characteristics, enhanced cellular uptake in high CD44-expressing cells, and potent inhibitory effects on migration, invasion, and epithelial-mesenchymal transition in BC cells. Long-term in vivo imaging illustrated sustained accumulation of PCL-NP@VP/siYAP in orthotopic bladder tumors, leading to diminished tumor volume and distant metastases. Ultimately, this nanotherapeutic approach effectively disrupted the YAP/TAZ/AXL axis, reversing the mechanical tumor microenvironment induced by pBOO-associated MS and presenting a promising strategy to impede BC progression and metastasis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149269092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itaconate-based hydrogels for immunomodulation and infection control: design strategies, biomedical applications, and translational challenges.","authors":"Min Wang, Jiachen Wang, Guoqiang Wang, Mi Chen, Jing An, Hao Yang","doi":"10.1186/s12951-026-04862-9","DOIUrl":"https://doi.org/10.1186/s12951-026-04862-9","url":null,"abstract":"<p><p>Itaconate is a bioactive immunometabolite with anti-inflammatory, antioxidant, and antimicrobial properties. Its unsaturated dicarboxylic structure allows for versatile polymerization and chemical functionalization. These characteristics make it a promising building block for bioactive hydrogels. However, current research on itaconate-based hydrogels is fragmented across immunology, polymer chemistry, and biomedical engineering, with a lack of a unified design framework. In this review, we summarize the biological properties of itaconate and its derivatives relevant to biomaterial design, including immunomodulatory effects and antimicrobial activity. We categorize itaconate-based hydrogels into two main strategies: those directly fabricated from itaconate or its analogues, and those loaded with itaconate or itaconate derivatives such as 4-octyl itaconate (4-OI) and dimethyl itaconate (DMI). We explore the relationships between composition, crosslinking chemistry, responsiveness, biological functions, and therapeutic applications in drug delivery, tissue repair, inflammatory diseases, and anti-infective therapy. We also highlight critical limitations, including insufficient structure-function comparisons, overreliance on small-animal models, limited mechanistic validation, and challenges in manufacturing, stability, biosafety, and clinical translation. This review presents a conceptual framework for the rational design of itaconate-based hydrogels and outlines key priorities for advancing these materials toward clinical translation as bioactive and immunomodulatory hydrogel platforms.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149268949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrophobic nano-calcium superphosphate enhances leaf disease resistance via coordinated physical, biochemical, and phyllosphere responses.","authors":"Tao He, Mingxin Fu, Meijing Wang, Meng Yang, Mei Li, Ronghui Du, Rongqi Lin, Weiping Deng, Min Yang, Airong Li, Shusheng Zhu, Fei Du","doi":"10.1186/s12951-026-04828-x","DOIUrl":"10.1186/s12951-026-04828-x","url":null,"abstract":"<p><p>Hydrophobic nano-calcium superphosphate (NPS1) is a novel nano-fertilizer that has shown great potential for enhancing plant growth and suppressing foliar diseases. However, the mechanisms underlying these effects remain unclear. We investigated the responses of grape leaves and phyllosphere microbiota to NPS1 under both open-field and rain-shelter cultivation systems. NPS1 application significantly reduced leaf wetness duration and the disease severity of downy and powdery mildew, increased leaf-associated phosphorus retention, which remained elevated at later sampling stages, while enhancing vine growth, increasing SOD and POD activities, and inhibits several grape pathogens in vitro. Integrated transcriptomic and metabolomic analyses identified substantial changes in gene expression and metabolite accumulation following NPS1 treatment, characterized by the upregulation of stress-responsive genes (WRKY41, PEROXIDASE, and EREBP) and enrichment of pathways related to phenylpropanoid and secondary metabolite biosynthesis. Exogenous validation experiments indicated that coumaric acid and lignin were associated with enhanced seedling growth and restricted pathogen growth in vitro. Furthermore, amplicon sequencing revealed significant shifts in the composition, diversity, and co-occurrence patterns of phyllosphere microbial communities, accompanied by reduced relative abundances of pathogen-associated taxa (e.g., Erysiphe and oomycetes). Notably, representative beneficial isolates (e.g., Sphingomonas spp. and Bacillus spp.) exhibited stronger pathogen inhibition when combined with NPS1 than when applied alone. Collectively, these findings indicate that NPS1 alters the leaf surface conditions through reduced leaf wetness, associated with coordinated changes in plant physiological responses, metabolite accumulation, and phyllosphere microbial communities, which may be linked to reduced disease severity and improved grapevine performance.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory 3D-printed conductive scaffold combined with electrostimulation: a dual-strategy approach to enhance bone regeneration.","authors":"Lijuan Wang, Chenxu Wang, Dejian Li, Xiaojun Zhou, Chuanglong He","doi":"10.1186/s12951-026-04784-6","DOIUrl":"https://doi.org/10.1186/s12951-026-04784-6","url":null,"abstract":"<p><p>Conventional conductive scaffolds lack the capacity to dynamically coordinate the immuno-osteogenic coupling that is critical for effective bone repair. In this study, we developed a three-dimensional (3D) printed immunomodulatory conductive scaffold that integrates anti-inflammatory macrophage induction with electrical signal transmission. This scaffold achieves a combination of available electrical conductivity and immunomodulatory function through poly(3,4-ethylenedioxythiophene) (PEDOT) doping and controlled ion release. In vitro experiments demonstrated that the scaffold enhanced M2 macrophage polarization by potential regulation of the NF-κB signaling pathway mediated by bioactive ions, even under conditions of electrical stimulation (ES). Furthermore, it synergistically promoted the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the presence of ES. In vivo evaluation using a rat cranial defect model revealed that the scaffold combined with ES accelerated bone regeneration via the convergence of immunomodulation and electrical cues, as evidenced by coordinated M2 macrophage infiltration and early angiogenesis. This study provides a promising strategy that integrates conductive network and bioactive ion release to establish an electrostimulation and immunoregulation microenvironment for the treatment of bone defect.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149268946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS-responsive injectable hydrogel enables controlled release of human adipose tissue-derived extracellular vesicles for multifaceted osteoarthritis therapy.","authors":"Yikai Wang, Le Kang, Kaizhe Chen, Yu Jiang, Yi Zheng, Peng Xu, Chuandong Wang, Wenhui Zhu, Dequn Wu, Kai Liu","doi":"10.1186/s12951-026-04838-9","DOIUrl":"10.1186/s12951-026-04838-9","url":null,"abstract":"<p><p>Chronic inflammation and elevated reactive oxygen species (ROS) are pivotal drivers of osteoarthritis (OA), demanding integrated, pathology-adaptive strategies. Here, we develop an injectable, ROS-responsive hydrogel for intra-articular delivery of human adipose tissue-derived extracellular vesicles (AT-EVs) to enable multifaceted OA treatment. Unlike conventional cell-derived MSC-EVs, AT-EVs are tissue-derived and can be isolated directly from lipoaspirate under aseptic operating-room conditions, providing a clinically practical EV source that bypasses prolonged cell expansion and multi-step culture conditioning. Small RNA-seq established their OA therapeutic potential. To facilitate intra-articular retention, the AT-EVs@BA-CS/EGCG hydrogel is formed via dynamic boronate ester crosslinking between phenylboronic acid-grafted chitosan and epigallocatechin-3-gallate (EGCG), achieving triple functionality: (i) injectable self-healing capacity, (ii) ROS-triggered controlled release, and (iii) synergistic ROS scavenging capacity. In vitro, the hydrogel attenuated oxidative stress, protected chondrocytes, restored matrix homeostasis, and suppressed inflammatory macrophage activation. Integrated small RNA profiling, transcriptomics, and phospho-protein validation consistently implicated PI3K/AKT/mTOR pathway modulation as a key mechanism. In a rat OA model, AT-EVs@BA-CS/EGCG mitigated cartilage degeneration, reduced oxidative damage, and dampened inflammatory macrophage signatures. Collectively, this study provides a clinically practical, ROS-adaptive EV-hydrogel platform with translational potential for OA therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}