Journal of Nanobiotechnology最新文献

{"title":"Discriminating single-amino acid differences and post-translational modifications in negatively charged peptides with α-hemolysin nanopores.","authors":"Liting Kang, Linting Wang, Xuefei Fan, Lingfang Xu, Han Yang, Chenxin Wu, Tongxin Zhu, Xiangyi Zhao, Linming Zhang, Jianhuang Xue, Shuanghong Yan","doi":"10.1186/s12951-026-04818-z","DOIUrl":"https://doi.org/10.1186/s12951-026-04818-z","url":null,"abstract":"<p><p>Effective and precise detection of peptides and their post-translational modifications (PTMs) is crucial for biomedical research but remains technically challenging. Here, we present a nanopore sensing strategy that enables label-free analysis of negatively charged peptides. By introducing arginine residues into the nanopore and using amino-cyclodextrin as a molecular adaptor, the system enables unambiguous discrimination of short negatively charged homopeptides differing by only a single residue. Building on this capability, the platform further demonstrates high sensitivity for detecting representative PTMs, including acetylation, lactylation, and phosphorylation, introduced on a negatively charged peptide scaffold. Notably, the system could also analyze fragments generated by proteolytic digestion of full-length proteins, underscoring its potential for accurate protein identification. This work offers an accessible and reliable strategy to characterize peptide variants with single-amino acid differences and PTMs, which may facilitate future applications in peptide biomarker detection and protein sequence analysis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549567","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":"Virosome-masked ratiometric nanoprobes for in vivo dynamic imaging of influenza a virus infection.","authors":"Ruiqi Ming, Yue Wang, Zewei Yan, Shujun Liu, Zhongjie Wang, Hanlin Chen, Yingjie Shi, Yuantian Jing, Rui Zhang, Shasha Peng, Jiajie Tian, Yimei Pan, Wenfeng Xu, Pengfei Jin, Li-Li Huang","doi":"10.1186/s12951-026-04819-y","DOIUrl":"https://doi.org/10.1186/s12951-026-04819-y","url":null,"abstract":"<p><p>In vivo fluorescent in situ visualization of viral infection dynamics is crucial for elucidating the mechanisms of viral pathogenesis. However, current approaches lack sufficient specificity and sensitivity for spatiotemporal monitoring of viral infection in vivo. Here, we proposed virosome-masked ratiometric nanoprobes (VMR-NPs) integrated with dual-stimuli-responsive near-infrared (NIR) Förster resonance energy transfer (FRET) reporters that specifically recognize influenza A virus (IAV) viral RNA (vRNA) and apurinic/apyrimidinic endonuclease 1 (APE1). Surface hemagglutinin (HA) envelope protein of IAV virosome endows VMR-NPs with enhanced host-cell association and IAV-like intracellular trafficking behavior. Following internalization, vRNA recognition together with APE1-assisted signal amplification modulates the ratiometric fluorescence output of VMR-NPs, enabling sensitive detection of infection-associated signal changes in vitro and in vivo. This study establishes an IAV virosome-masked sensing platform for imaging infection-associated IAV burden and provides a useful tool for studying virus-related biological processes.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549528","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":"An integrative multi-omics landscape of multi-dimensional cellular stress and metabolic reprogramming in melanoma treated with targeted alpha therapy.","authors":"Jiajia Zhang, Zhiling Song, Zhengguo Chen, Xiaohui Luan, Yuying Yu, Xuhao Huang, Jie Lye, Jianguo Li, Jie Gao, Yuanyou Yang, Kazuya Kabayama, Koichi Fukase, Ning Liu, Feize Li, Fei Yu","doi":"10.1186/s12951-026-04808-1","DOIUrl":"https://doi.org/10.1186/s12951-026-04808-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the biological mechanisms underlying the therapeutic effects of targeted alpha therapy (TAT) using a novel ²¹¹At-labeled single-domain antibody drug ([²¹¹At]At-AuNP-sdAb). By integrating transcriptomic and metabolomic analyses, we sought to characterize the coordinated gene-metabolite responses induced by α-particle irradiation in melanoma models.</p><p><strong>Methods: </strong>B16F10 melanoma cells and tumor-bearing mice were treated with [²¹¹At]At-AuNP-sdAb. RNA sequencing and untargeted LC-MS metabolomics were performed to identify differentially expressed genes and metabolites. Functional enrichment, OPLS-DA modeling, ROC curve analysis, and O2PLS-based multi-omics integration were used to explore the molecular networks and candidate indicators.</p><p><strong>Results: </strong>[²¹¹At]At-AuNP-sdAb treatment significantly altered the transcription of 777 genes, revealing multi-dimensional cellular stress responses encompassing coordinated nuclear-cytoplasmic perturbations alongside downstream alterations in the mitochondrial respirasome and endoplasmic reticulum homeostasis. Untargeted metabolomic profiling revealed extensive metabolic reprogramming across amino acid, nucleotide, and lipid pathways, identifying key potential candidate indicators such as L-dihydroorotate, and Betaine. Furthermore, O2PLS integration successfully decoded robust multi-system covariance networks, wherein candidate distal metabolic nodes like glucosamine-6-phosphate demonstrated strong correlations with gene clusters regulating microenvironment remodeling.</p><p><strong>Conclusion: </strong>[²¹¹At]At-AuNP-sdAb induces multi-dimensional cellular stress and extensive metabolic reprogramming characterized by concurrent genomic damage, subcellular organelle perturbations, and microenvironmental remodeling. The decoded multi-omics covariance networks and specific candidate indicators provide a comprehensive molecular landscape of α-particle-induced biological responses, offering valuable candidate frameworks for monitoring and evaluating TAT therapeutic outcomes.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536308","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":"Colon-targeting pH-responsive Bletilla striata polysaccharide coacervate microdroplets for ulcerative colitis therapy via macrophage reprogramming.","authors":"Qiantao Zhang, Lai Chai, Hui Liu, Xueer Hu, Yujing Niu, Hongli Cao, Xin Rao, Mingyuan Zhou, Yuchi Chen, Xiaoqing Ye, Fangmei Zhou, Zhishan Ding, Bingqi Zhu","doi":"10.1186/s12951-026-04824-1","DOIUrl":"10.1186/s12951-026-04824-1","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is an immune-mediated chronic inflammatory bowel disease that severely impairs patients' quality of life. Efficient oral colon-targeted delivery systems are urgently needed to improve local therapeutic efficacy while minimizing systemic exposure. Herein, we developed a pH-responsive Eudragit S100-coated coacervate microdroplet system for the oral delivery of natural Bletilla striata polysaccharide (BSP), termed BSP@EU-Coac. The optimized BSP@EU-Coac microdroplets exhibited a spherical morphology with an average hydrodynamic diameter of 3.86 ± 0.82 μm, an encapsulation efficiency of 85.03 ± 3.66%, and a drug loading capacity of 9.29 ± 0.93%. In vitro release studies showed that BSP@EU-Coac effectively limited premature BSP release under simulated gastric and small intestinal conditions, while achieving pH-triggered sustained release in simulated colonic medium, with a cumulative release of approximately 88.25% within 96 h. In vitro assays further demonstrated that BSP@EU-Coac showed good cytocompatibility at the working concentration and markedly reduced intracellular ROS levels, with ROS fluorescence intensity decreased by 53.95% and 51.13% in RAW264.7 macrophages and Caco-2 cells, respectively. After oral administration, fluorescence imaging confirmed that BSP@EU-Coac preferentially accumulated in the inflamed colon and maintained detectable colonic retention for up to 24 h. In a DSS-induced colitis mouse model, BSP@EU-Coac significantly alleviated UC symptoms, as evidenced by improved body weight recovery, reduced disease activity index, and restoration of colon length from 4.99 ± 1.23 cm in the model group to 8.66 ± 1.92 cm. Mechanistically, BSP@EU-Coac modulated macrophage polarization by reducing the M1-like CD86⁺CD206⁻ population from 29.26% to 8.95% and increasing the M2-like CD86⁻CD206⁺ population to 20.70%, accompanied by suppressed pro-inflammatory cytokine expression, enhanced tight junction protein expression, reduced oxidative stress, and partial restoration of gut microbiota homeostasis. Overall, this study demonstrates that BSP@EU-Coac is a promising oral colon-targeted polysaccharide delivery platform for UC therapy through integrated regulation of oxidative stress, immune response, epithelial barrier repair, and gut microbiota.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536232","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":"Quaternary ammonium carbon dots for membrane perforation-immunity synergistic therapy against drug-resistant cancer metastasis.","authors":"Qi Wu, Shanshan Wang, Jingchun Wang, Siran Jin, Yikai Ma, Xiaodan Wu, Jing Liu, Hui Zhang, Guanghui Tan, Yingxue Jin","doi":"10.1186/s12951-026-04815-2","DOIUrl":"10.1186/s12951-026-04815-2","url":null,"abstract":"<p><p>Multidrug resistance and invasive metastasis constitute pivotal clinical bottlenecks that severely compromise curative outcomes of malignant tumors. Conventional chemotherapy and immunotherapy frequently fail to achieve satisfactory efficacy due to drug resistance barriers and tumor immune escape. Herein, a hyaluronic acid‑cinnamaldehyde Schiff base micelle nanoplatform loading quaternary ammonium‑modified carbon dots (HACA@QASCDs) is rationally constructed, which achieves targeted killing of drug‑resistant tumor cells, remodeling of immunosuppressive microenvironments, and inhibition of distant metastasis via a sequential cascade of irreversible membrane perforation, mitochondria‑dependent apoptosis, and immunogenic cell death (ICD). HACA@QASCDs actively accumulate in drug‑resistant CT26 (DR‑CT26) cells through HA‑CD44 recognition and enable pH‑triggered QASCDs release in acidic tumor microenvironments. The liberated QASCDs elicit irreversible membrane perforation, leading to lactate dehydrogenase leakage, disrupted calcium homeostasis, mitochondrial depolarization, and subsequent intrinsic apoptosis. Such membrane damage simultaneously ignites ICD, and the released damage‑associated molecular patterns effectively drive dendritic cell maturation and M2‑to‑M1 macrophage polarization. In vivo evaluations in bilateral syngeneic tumor models reveal that HACA@QASCDs alone yields 54.2% primary tumor inhibition and 28.6% distant tumor inhibition. Upon combination with αPD‑L1, the distant tumor inhibition rate is markedly elevated to 68.7%. By integrating membrane perforation‑mediated direct cytotoxicity and ICD‑evoked immune activation, HACA@QASCDs offers a highly potent and clinically translatable synergistic strategy to surmount tumor multidrug resistance and block invasive metastasis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497640","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":"ROS-scavenging microspheres loaded with extracellular vesicles for intervertebral disc degeneration therapy.","authors":"Chunping A, Haozhe Cheng, Guangzi Chen, Chuang Huang, Lice Wang, Kai Cao, Tao Xu, Zhong Fang","doi":"10.1186/s12951-026-04740-4","DOIUrl":"https://doi.org/10.1186/s12951-026-04740-4","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD), primarily driven by oxidative stress and inflammation, significantly impacts patient quality of life. Current therapies lack efficacy, highlighting the need for novel treatment strategies. This study investigates the protective effect of antioxidant hydrogel microspheres containing black phosphorus (BP) nanosheets and extracellular vesicles (EVs), fabricated using a microfluidic technology-based delivery system, designated as EVs@BPMS. In vitro analyses of EVs@BPMS revealed that BP nanosheets enhanced the antioxidant capacity of the hydrogel microspheres. The EVs@BPMS system functioned through the sustained release of extracellular vesicles. These vesicles collectively mitigated oxidative damage by scavenging reactive oxygen species (ROS), reducing oxidative stress, suppressing cellular senescence, and ultimately restoring extracellular matrix homeostasis in nucleus pulposus cells. Transcriptomic analysis further elucidated that the microspheres inhibited inflammatory responses via the IL-17-ferroptosis pathway, providing a theoretical basis for the development of targeted therapeutic interventions. In vivo studies confirmed the protective efficacy of EVs@BPMS in a rat model of IVDD, demonstrating substantial attenuation of disc degeneration. The findings underscored the innovative capacity of antioxidant hydrogel microspheres in regulating oxidative stress and maintaining cellular homeostasis. Moreover, they highlighted the potential of these microspheres for clinical application in degenerative disc disease.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497629","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":"Emerging role of herbal nanogel formulations in skin cancer therapy: mechanistic insights and translational advances in nanomedicine.","authors":"Suraj Kumar, Rishabha Malviya, Phool Chandra, Sathvik Belagodu Sridhar, Javedh Shareef, Tarun Wadhwa, Daniel Arockiam","doi":"10.1186/s12951-026-04788-2","DOIUrl":"https://doi.org/10.1186/s12951-026-04788-2","url":null,"abstract":"<p><strong>Objective: </strong>Skin cancer remains a major global health concern, necessitating the development of innovative therapeutic strategies that enhance treatment efficacy while minimizing adverse effects. This review aims to explore the emerging role of herbal nanogels as a promising nanotechnology-based drug delivery system for skin cancer therapy.</p><p><strong>Methods: </strong>A comprehensive review of recent literature was conducted focusing on nanogel-based drug delivery systems, herbal bioactive compounds, and stimulus-responsive nanotechnology approaches for cancer treatment, particularly skin cancer.</p><p><strong>Results: </strong>Nanogels, defined as crosslinked nanoscale polymeric networks, have gained significant attention due to their high drug-loading capacity, tunable physicochemical properties, and ability to respond to various internal and external stimuli. They can be synthesized using techniques such as emulsion methods, micro-molding, and photolithography, allowing precise control over size and morphology. Advanced stimulus-responsive nanogels, including tumor microenvironment-sensitive and ligand-targeted systems (e.g., LHRH-targeted nanogels), enable controlled and site-specific drug release. Recent developments in herbal nanogels integrate plant-derived bioactive compounds within nanogel matrices, enhancing solubility, stability, and therapeutic efficiency against skin cancer.</p><p><strong>Discussion: </strong>Herbal nanogels represent a promising interdisciplinary approach combining nanotechnology and phytomedicine, offering targeted, less invasive, and potentially more effective treatment options for skin cancer. Despite significant progress, challenges such as clinical translation, large-scale production, and long-term safety evaluation remain. Continued research in smart and multifunctional nanogel systems may significantly advance future skin cancer therapies.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471140","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":"Gut-derived extracellular vesicle enriched miR-125a-5p mediates cadmium-induced intestinal injury through NF-κB pathway activation.","authors":"Mengzhen Song, Lina Ping, Yulin Wang, Wenjun Zhou, Jinping Fan, Shiyu Tao, Yaoqin Shen","doi":"10.1186/s12951-026-04809-0","DOIUrl":"https://doi.org/10.1186/s12951-026-04809-0","url":null,"abstract":"<p><p>Cadmium (Cd), as a prevalent environmental heavy metal pollutant, has an incompletely elucidated mechanism of intestinal toxicity following oral ingestion. This study aims to elucidate novel mechanisms underlying cadmium-induced intestinal injury. By establishing a murine model of cadmium exposure, it was found that cadmium not only directly disrupts the intestinal barrier structure but also induces intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) experiments confirmed that the dysbiotic microbiota alone is sufficient to provoke intestinal injury, indicating that microbial dysregulation serves as a critical amplifier of cadmium toxicity. Further investigation revealed that cadmium exposure reshapes the intestinal microenvironment and alters the miRNA profile of gut-derived extracellular vesicles (EVs), with miR-125a-5p being significantly enriched in EVs from the cadmium-exposed group. Mechanistically, miR-125a-5p directly targets and suppresses TNFAIP3, a negative regulator of the NF-κB pathway, thereby relieving the inhibition of this signaling axis and driving sustained inflammation and barrier dysfunction, while inhibition of miR-125a-5p effectively blocks this toxic effect. This study is the first to delineate the axis of \"cadmium exposure - intestinal microbiota dysbiosis - gut EV - miR-125a-5p - TNFAIP3 - NF-κB pathway activation - intestinal injury\", providing new insights for the development of biomarkers and targeted interventions for cadmium-related intestinal disorders.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471220","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":"Inactivation of the leukemia inhibitory factor/signal transducer and activator of transcription 3 pathway: a pivotal mechanism in adenomyosis-related embryo implantation failure.","authors":"Qianru Dou, Zhengjie Han, Wenxiao Shao, Yongli Liu, Shenghui Yao, Yingying Qiu","doi":"10.1186/s12951-026-04505-z","DOIUrl":"https://doi.org/10.1186/s12951-026-04505-z","url":null,"abstract":"<p><strong>Background: </strong>Adenomyosis (AM) is frequently associated with compromised embryo implantation. The leukemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for endometrial receptivity; however, its mechanistic role in AM-related implantation failure remains insufficiently elucidated. This study aimed to investigate the inactivation mechanism of the LIF/STAT3 pathway in AM and to evaluate a novel nanotherapeutic strategy for restoring implantation capacity.</p><p><strong>Methods: </strong>Clinical endometrial samples from AM patients and controls were analyzed. A three-dimensional (3D) co-culture system simulating the endometrial microenvironment was established. Interventions were performed using a tofacitinib-loaded biomimetic nanogel (Tofa-NG). Comprehensive analyses included bulk RNA Sequencing (RNA-seq), immunohistochemistry (IHC), RT-qPCR, proteomics, inflammatory cytokine profiling, and metabolomics to dissect the pathological links.</p><p><strong>Results: </strong>The LIF/STAT3 signaling pathway was significantly downregulated in the endometrium of AM patients, correlating directly with implantation failure. Pathologically elevated inflammatory cytokines suppressed LIF expression via NF-κB pathway activation, exacerbating the inflammatory microenvironment. Metabolomic profiling revealed a strong association between LIF/STAT3 pathway inactivation and aberrant cellular energy metabolism. The engineered Tofa-NG facilitated targeted drug delivery, effectively mitigated local inflammation, and successfully reactivated the LIF/STAT3 pathway. Consequently, this intervention significantly improved the embryo implantation success rate in the experimental model.</p><p><strong>Conclusion: </strong>This study identifies the inactivation of the LIF/STAT3 pathway as a central mechanism underlying embryo implantation defects in AM, intricately linked to chronic inflammation and metabolic dysregulation. The Tofa-NG strategy demonstrates promising therapeutic potential by rectifying the signaling deficit and ameliorating the endometrial microenvironment. These findings provide a novel theoretical foundation for developing targeted, personalized treatments for infertility associated with AM.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497665","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":"Kidney‑enriched lipid nanoparticles delivering ANXA2 alleviate renal ischemia-reperfusion injury via CHMP2A-mediated necroptosis inhibition.","authors":"Dong Lai, Qing Bi, Jichen Wang, Weihao Chen, Shouqing Cao, Huaikang Li, Hao Gong, Shangwei Li, Xu Zhang, Huayi Feng, Xiubin Li, Junnan Xu","doi":"10.1186/s12951-026-04812-5","DOIUrl":"https://doi.org/10.1186/s12951-026-04812-5","url":null,"abstract":"<p><strong>Background: </strong>Renal ischemia-reperfusion injury (IRI) is a major complication following nephron-sparing surgery, with limited preventive strategies. Annexin A2 (ANXA2) is upregulated after renal IRI, but its functional role and therapeutic potential remain unclear.</p><p><strong>Methods: </strong>Utilizing ANXA2 knockout (KO) and wild-type mice subjected to renal IRI, we assessed injury, fibrosis, and cell death pathways. In vitro studies employed mouse renal tubular epithelial cells (TECs) with ANXA2 or charged multivesicular body protein (CHMP) 2A knockdown or overexpression. Molecular mechanisms were investigated via co-immunoprecipitation, mass spectrometry, and immunofluorescence. The Kidney-Targeting Peptide (KTP)-conjugated, ANXA2-loaded lipid nanoparticle (KTP-LNP@ANXA2) was synthesized and characterized. Its efficacy was evaluated in vitro and in a mouse renal IRI model.</p><p><strong>Results: </strong>ANXA2 was significantly upregulated post-IRI, predominantly in the renal medulla. KO mice exhibited exacerbated medullary injury, increased fibrosis, and enhanced necroptosis, as indicated by elevated phosphorylated MLKL (p‑MLKL) levels and severe apical membrane disruption, whereas no genotype‑dependent differences were detected in the selected markers of apoptosis, pyroptosis, or ferroptosis at 24 h. ANXA2 deficiency amplified the inflammatory response, increasing neutrophil infiltration through the upregulation of C-X-C motif chemokine ligand (CXCL) 1 and CXCL2. Mechanistically, ANXA2 associated with CHMP2A, a component of the endosomal sorting complex required for transport (ESCRT)-III membrane repair complex, following IRI, promoting ESCRT-III assembly at the apical membrane to counteract necroptosis. Knocking down CHMP2A abolished the protective effect of ANXA2. The engineered KTP-LNP@ANXA2 demonstrated excellent stability, biocompatibility, and enhanced uptake by renal TECs. Pre-treatment with KTP-LNP@ANXA2 in mice effectively delivered ANXA2 to the kidneys, attenuated IRI severity, reduced necroptosis and inflammation, and diminished neutrophil recruitment.</p><p><strong>Conclusion: </strong>ANXA2 confers protection against renal IRI by interacting with CHMP2A to facilitate ESCRT-III-mediated inhibition of TEC necroptosis, thereby attenuating subsequent inflammation. Enhancement of renal ANXA2 levels via engineered LNPs represents a novel and promising therapeutic strategy for preventing renal IRI.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497658","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}