{"title":"Bispecific self-assembled peptides as supra-growth factors for preventing endotheliopathy and improving survival of traumatic brain injury in mice.","authors":"Yichi Zhang, Lanxing Wang, Dandan Li, Xingyao Sun, Zijian Zhou, Ying Zhang, Linan Jiao, Shuhong Yang, Yafan Liu, Tianrui Ma, Hao Zhang, Lujia Tang, Kaifeng Pang, Pengbo Zhao, Muyan Xu, Jie Li, Jianning Zhang, Zhimou Yang, Jie Gao, Zilong Zhao","doi":"10.1186/s12951-025-03713-3","DOIUrl":"https://doi.org/10.1186/s12951-025-03713-3","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) causes endothelial injury (endotheliopathy), which contributes to a cascade of adverse events, including cerebral hemorrhage, edema and acute lung injury (ALI), and leads to poor clinical outcomes. Protecting endothelial integrity and targeting cerebral endothelium is therefore critical for preventing secondary cerebral injuries from TBI. However, effective treatment strategies in the clinic remain lacking. Here, we report a nanofiber of bispecific self-assembled peptide (BsSA) as a supra-growth factor that possesses multiple functions, such as binding to the blood‒brain barrier (BBB) and dual growth factor activity. BsSA protects TBI mice by binding to the BBB through Insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) and ameliorating endothelial injury by activating the IGF-1R/IR signaling pathway. Specifically, this protection is achieved by promoting endothelial cell proliferation and survival and mitigating oxidative stress. Exogenous BsSA, as a therapeutic agent, prevented mice with TBI from developing brain and pulmonary endotheliopathy and improved their outcomes. This study identified BsSA as a potential therapeutic agent to reduce TBI-induced endotheliopathy, brain edema, and lung injury and improve TBI outcomes.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"632"},"PeriodicalIF":12.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258367","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}
Jiayuan Qu, Jiayue Zeng, Li Mou, Xiaobin Wu, Mei Ha, Changjiang Liu
{"title":"Plastic tableware use, microplastic accumulation, and sperm quality: from epidemiological evidence to FOXA1/p38 mechanistic insights.","authors":"Jiayuan Qu, Jiayue Zeng, Li Mou, Xiaobin Wu, Mei Ha, Changjiang Liu","doi":"10.1186/s12951-025-03747-7","DOIUrl":"https://doi.org/10.1186/s12951-025-03747-7","url":null,"abstract":"<p><p>Microplastics (MPs), as emerging contaminants, may adversely affect male reproductive health. This study investigated the potential association between MP accumulation in human semen and sperm quality. Furthermore, the molecular mechanisms underlying MPs-induced sperm quality impairment were characterized using representative polystyrene microplastics (PS-MPs), murine models, and spermatogonial cell cultures. Among 200 semen samples, the overall detection rate of MPs was 55.5% (111/200). A total of 128 MPs were identified in semen, with PS (32.03%) and PVC (36.72%) being the predominant microplastic polymers. Epidemiological analyses revealed a significant positive association between plastic tableware (PT) use frequency and MP accumulation in semen. Stratified analyses further revealed a strong association between total MPs exposure and reduced sperm concentration among individuals with BMI < 24 kg/m² and frequent PT use. In murine models, exposure to PS-MPs induced reduced sperm quality, elevated sperm abnormalities, and increased levels of autophagy and apoptosis. Mechanistically, PS-MPs activated the MAP3K1/p38/c-fos pathway via the transcription factor FOXA1, thereby inducing the autophagy and apoptosis of spermatogonia. Collectively, this study provides direct human evidence that MP accumulation in semen is associated with impaired sperm quality, particularly in individuals with certain lifestyle factors such as frequent PT use. Moreover, our findings further demonstrate the potential reproductive toxicity of MPs and, for the first time, elucidate the critical role of the FOXA1/MAP3K1/p38 cascade in PS-MPs-mediated decline in sperm quality.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"634"},"PeriodicalIF":12.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258452","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}
Sri Ganga Padaga, Milan Paul, Tonmoy Banerjee, Saptami Goswami, Balaram Ghosh, Swati Biswas
{"title":"Hybrid metallic nanozyme with nitric oxide-releasing photothermal coating for accelerated infected diabetic wound healing.","authors":"Sri Ganga Padaga, Milan Paul, Tonmoy Banerjee, Saptami Goswami, Balaram Ghosh, Swati Biswas","doi":"10.1186/s12951-025-03693-4","DOIUrl":"https://doi.org/10.1186/s12951-025-03693-4","url":null,"abstract":"<p><p>Infected diabetic wounds are prone to developing bacterial biofilms and are difficult to treat due to a lack of strategies that can eliminate drug-resistant bacteria. Conventional antibiotics can't achieve the desired antibacterial effect due to their limited penetration into the biofilm, which makes the treatment challenging. In this study, we developed NIR-responsive nitric oxide (NO) releasing Ce: Zn nanoflowers (PDA@SNP@Ce:Zn NFs) to combat the drug-resistant bacteria by the synergistic antibacterial effect of metal ions and photothermal effect. PDA@SNP@Ce:Zn NFs exhibited significant antibacterial and antibiofilm effects against Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA). The nanoflowers exhibited significant inhibitory effects on the virulence of MRSA and SA, including spreading motility, secretion of phenol-soluble modulin proteins, and staphyloxanthin, after laser irradiation. The PDA@SNP@Ce:Zn NFs were able to cause membrane disruption and eradicate the MRSA and SA biofilms that were analyzed by scanning electron microscope. Additionally, these nanoflowers significantly accelerated wound healing in MRSA-infected diabetic rats by reducing the inflammation and promoting angiogenesis at the wound site. Our findings suggested that the developed photothermal nanoflower system would be an alternate approach to prevent drug-resistant bacterial infections.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"630"},"PeriodicalIF":12.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258311","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}
Ge Bai, Hongwen Liu, Wei Li, Sijia Chen, Lishan Wang, Zhangding Wang, Yue Zhou, Yani Pan, Yu Liu, Qi Chen, Nannan Zhang, Jingjing Wei, Xueni Fu, Yaru Zhou, Yun Zhu, Lei Xu, Lei Wang
{"title":"Mitochondria-targeting polymer cLipG/CuET activates the cGAS/STING pathway to enhance cholangiocarcinoma immunotherapy.","authors":"Ge Bai, Hongwen Liu, Wei Li, Sijia Chen, Lishan Wang, Zhangding Wang, Yue Zhou, Yani Pan, Yu Liu, Qi Chen, Nannan Zhang, Jingjing Wei, Xueni Fu, Yaru Zhou, Yun Zhu, Lei Xu, Lei Wang","doi":"10.1186/s12951-025-03689-0","DOIUrl":"https://doi.org/10.1186/s12951-025-03689-0","url":null,"abstract":"<p><strong>Background: </strong>The remodeling of extracellular matrix often fails chemotherapeutic agents to fight intrahepatic cholangiocarcinoma (ICC). The cGAS/STING pathway can trigger the innate immune response to obtain better immunotherapeutic outcomes.</p><p><strong>Results: </strong>A cLipG/CuET nanocomposite was designed and synthesized based on glycyrrhizic acid (GA) and copper diethyldithiocarbamate (CuET). GA can open mitochondrial permeability transition pores (MPTPs), allowing Cu (II) to interrupt mitochondrial function through copper toxicity. By activating the cGAS-STING signaling pathway in macrophages, this mitochondrial-targeting polymer (cLipG/CuET) significantly boosted the production of mitochondrial reactive oxygen species (mtROS), and promoted the escape of damaged mitochondrial DNA (mtDNA) from ICC cells. Consequently, M1 polarization of cancer-associated macrophages enhanced the immune response against ICC. In the mouse model, the intravenous administration of cLipG/CuET transformed the ICC from \"cold\" into \"hot\".</p><p><strong>Conclusions: </strong>With a high biosafety, cLipG/CuET exerted a synergistic effect on the immune checkpoint inhibitor αCTLA-4 against ICC, and their combination provided a new therapeutic strategy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"631"},"PeriodicalIF":12.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258324","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}
Zhenlong Mu, Yang Chen, Yunfeng Hu, Hui Wang, Jin Li
{"title":"Tailored brain metastatic tumor cells-derived apoptotic bodies ameliorate Alzheimer's disease by promoting microglia efferocytosis and neuroinflammation mitigation.","authors":"Zhenlong Mu, Yang Chen, Yunfeng Hu, Hui Wang, Jin Li","doi":"10.1186/s12951-025-03750-y","DOIUrl":"https://doi.org/10.1186/s12951-025-03750-y","url":null,"abstract":"<p><p>Neuroinflammation, characterized by microglial overactivation and oxidative stress, plays a critical role in the initiation and progression of Alzheimer's disease (AD). In this study, we focus on simulating the natural efferocytosis process to reprogram microglial and mitigate chronic neuroinflammation for combinational AD therapy. To achieve this goal, engineered apoptotic bodies derived from brain metastatic tumor cells (LAbs) are successfully developed. Specifically, LAbs-based nanocomposites were fabricated by hybridizing LAbs with liposomes co-loaded with manganese dioxide nanoenzyme (BMn) and autophagy-activating rapamycin (Rapa), referred to as LAbs@Lip@BMn/Rapa. LAbs@Lip@BMn/Rapa exhibits efficient BBB penetration via LAbs-associated brain metastasis propensity of apoptotic bodies. Within the AD microenvironment, oxygen produced through BMn catalyzation in response to H<sub>2</sub>O<sub>2</sub> triggers the structural disintegration of LAbs-camouflaged liposomes and their reassembly into ultra-small vesicles, thereby significantly enhancing intracranial delivery efficiency. In vitro and in vivo experiments confirm that this multi-target strategy effectively normalizes microglia toward anti-inflammatory M2 phenotype, scavenges reactive oxide species (ROS) accumulation, promotes β-amyloid and phosphorylated tau clearance through synergistic intervention, restores the pathological microenvironment in the brain, and enhances cognitive functions in AD model mice. This study demonstrates a novel LAbs-based biomimetic construction strategy that effectively penetrates the BBB and regulates microglia functions, offering a promising approach for AD treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"633"},"PeriodicalIF":12.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258415","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}
Tanja Dučić, Eva Pereiro, Milena Ninkovic, Swetlana Sperling, Veit Rohde, Claudia Fernández-González, Manuel Algarra, Elena González-Muñoz
{"title":"Single-cell in situ mapping of glioblastoma and astrocyte cell lines treated with a carbon dot-mediated riluzole nanotherapeutic agent: a live-cell µFTIR and soft X-ray tomography approach.","authors":"Tanja Dučić, Eva Pereiro, Milena Ninkovic, Swetlana Sperling, Veit Rohde, Claudia Fernández-González, Manuel Algarra, Elena González-Muñoz","doi":"10.1186/s12951-025-03687-2","DOIUrl":"10.1186/s12951-025-03687-2","url":null,"abstract":"<p><p>Nanoparticle-based drug carriers offer a promising alternative to conventional cancer therapies by enabling targeted delivery and reducing off-target toxicity. Here, we used synthesised and characterised carbon-based nanoparticles derived from 2-acrylamido-2-methylpropanesulfonic acid (AMPS-CDs), demonstrating biocompatibility with both human astrocytes and glioblastoma cells. We assessed their potential to enhance riluzole's efficacy through synergistic interaction (AMPS-CDs@RZ) using live-cell synchrotron-based FTIR spectroscopy and cryo-soft X-ray tomography to monitor biochemical and structural changes at the single-cell level. While AMPS-CDs nanoparticles alone were non-toxic, the combination with riluzole significantly enhanced cell death in glioblastoma cells, with a significantly lower impact in non-cancerous astrocytes. Treatment with AMPS-CDs@RZ induced significant changes in bio-macromolecules, including DNA, protein conformation, and lipid metabolism. Notably, the treatment triggered nuclear envelope (NE) blebbing in glioblastoma cells, likely due to the interaction of the nanoparticle formulation with the nuclear membrane. This initiated stress signals that disrupted the cell's inner intracellular membrane system, including the endoplasmic reticulum and mitochondria. To our knowledge, this is the first report linking NE blebbing to this mechanism involving membrane disassembly and nuclear envelope blebbing in riluzole-induced toxicity in glioblastoma is novel, providing a new therapeutic strategy and insights into cellular stress responses. These findings suggest that AMPS-CDs nanoparticles are a promising carrier for riluzole, potentially enhancing the specificity and efficacy of glioblastoma treatments while minimising damage to healthy tissues.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"629"},"PeriodicalIF":12.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238873","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":"Astragalus polysaccharide-based nano-platforms loading PTX to boost chemo-immunotherapy for triple-negative breast cancer with intrinsic GLUT-targeting ability and immunoregulatory activity.","authors":"Jinshuai Lan, Wenlong Nie, Zhijun Bi, Ruifeng Zeng, Zhe Li, Tong Zhang, Yue Ding","doi":"10.1186/s12951-025-03708-0","DOIUrl":"10.1186/s12951-025-03708-0","url":null,"abstract":"<p><p>Chemo-immunotherapy shows great promises for triple-negative breast cancer (TNBC) treatment, including PTX. However, the chemo-immunotherapy of PTX is limited, due to its upregulation of PD-L1 expression on tumor cells and bone marrow suppression. In addition, nano drug delivery systems of PTX encounter substantial challenges against tumors, such as inefficient encapsulation and inadequate tumor targeting efficacy. Here, PTX-loaded nanoparticles (APS-PTX NPs) based on astragalus polysaccharide (APS) was successfully developed to address these challenges. In APS-PTX NPs, APS could form amphiphilic polymers to highly load PTX, in which APS worked as the carrier, active targeting ligand, immunoregulator and chemotherapy adjuvant at the same time. Compared to PTX or Lipusu<sup>®</sup> (PTX-Lipo), APS-PTX NPs increased cellular uptake by binding to high expressed glucose transporter of 4T1 cells, and synergistically enhanced cytotoxicity of PTX. Meanwhile, APS-PTX NPs induced immunogenic cell death to induce DC maturation and decreased PD-L1 expression of 4T1 cells. In the TNBC model, APS-PTX NPs synergistically activates a potent systemic anti-tumor immunity, effectively inhibiting tumor growth and lung metastasis, and alleviating the reduction of white blood cell induced by PTX. Overall, the multifunctional nanoplatforms based on APS could overcome the harsh tumor biological barriers, and boost chemo-immunotherapy for TNBC treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"628"},"PeriodicalIF":12.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238850","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":"Engineering bispecific HER2xVEGF designed ankyrin repeat proteins for targeted nanobiotechnology applications.","authors":"Feng Chen, Michelle S Bradbury","doi":"10.1186/s12951-025-03631-4","DOIUrl":"10.1186/s12951-025-03631-4","url":null,"abstract":"<p><strong>Background: </strong>Targeting both tumor cell surface receptors and soluble pro-angiogenic factors is a promising strategy to improve cancer treatment specificity and reduce therapy resistance. Human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) are two clinically validated targets implicated in tumor growth, metastasis, and angiogenesis. To address limitations of conventional large-molecule therapeutics, we developed a modular bispecific protein scaffold based on Designed Ankyrin Repeat Proteins (DARPins) for precision nanobiotechnology applications.</p><p><strong>Results: </strong>We engineered a bispecific HER2×VEGF DARPin containing a C-terminal cysteine for site-specific bioorthogonal conjugation. The construct was recombinantly expressed in Escherichia coli and purified to high monomeric purity. Subsequent azide functionalization enabled strain-promoted click conjugation with diverse payloads, including fluorescent dyes for imaging, radionuclide chelators for diagnostic and therapeutic isotope labeling, and a cleavable drug linker for cytotoxic payload delivery. All bioconjugates retained high structural integrity and dual-specific binding affinity to HER2 and VEGF, with dissociation constants in the low picomolar to nanomolar range as measured by surface plasmon resonance. Importantly, site-specific conjugation did not impair antigen recognition, highlighting the robustness of the scaffold.</p><p><strong>Conclusions: </strong>This study presents a scalable and versatile bispecific DARPin platform that enables modular, site-specific conjugation of imaging and therapeutic payloads without loss of binding function. The preserved dual-targeting capability and biochemical stability make it a promising candidate for nanobiotechnology-based diagnostics, radiotherapy, and targeted drug delivery in precision oncology.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"627"},"PeriodicalIF":12.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228421","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}
Qihang Yan, Li Gong, Zihui Tan, Zining Liu, Xiaodong Li, Dachuan Liang, Jie Yang, Kai Zhang, Shuqin Dai, Junye Wang
{"title":"Targeting tumor microenvironment with biomimetic nanovesicles for non-small cell lung cancer gene therapy.","authors":"Qihang Yan, Li Gong, Zihui Tan, Zining Liu, Xiaodong Li, Dachuan Liang, Jie Yang, Kai Zhang, Shuqin Dai, Junye Wang","doi":"10.1186/s12951-025-03684-5","DOIUrl":"10.1186/s12951-025-03684-5","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, with therapeutic outcomes often constrained by the complexity of the tumor microenvironment (TME). Comprising diverse cell types and signaling molecules, the TME is increasingly recognized as a critical determinant of tumor behavior and patient prognosis. Cancer-associated fibroblasts (CAFs), a dominant TME component, drive progression through intercellular communication. Although CAF-targeted therapies hold promise, the precise mechanisms underlying CAF-cancer cell interactions remain elusive. Leveraging single-cell sequencing, we identified ACTN1 as a gene highly expressed in CAFs and strongly correlated with NSCLC prognosis. We engineered an integrated hybrid nanovesicle composed of CAF membranes (cM) and a liposome core to encapsulate siRNA against ACTN1 (siACTN1). This represents the first CAF-membrane-coated siRNA system targeting ACTN1 for NSCLC therapy. The nanovesicles modulate cytokine secretion (IL-6 and CCL2) to inhibit NSCLC cell growth, migration, and invasion in vitro. In vivo studies corroborated these findings, demonstrating reduced cytokine secretion and attenuated tumor growth. By harnessing the intrinsic properties of CAFs for targeted siRNA delivery, these nanovesicles offer a novel strategy for TME modulation in NSCLC.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"624"},"PeriodicalIF":12.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206561","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}
Yi Jin, Nengjie Yang, Siyu Chen, Yanan Wei, Xiangyu Wei, Yujuan Zhu, Chi Sun
{"title":"Bioinspired catalytic nanogel as an inflammatory cascade-targeted therapeutic for rheumatoid arthritis.","authors":"Yi Jin, Nengjie Yang, Siyu Chen, Yanan Wei, Xiangyu Wei, Yujuan Zhu, Chi Sun","doi":"10.1186/s12951-025-03642-1","DOIUrl":"10.1186/s12951-025-03642-1","url":null,"abstract":"<p><p>The inflammatory cascade is a key driver of chronic inflammation in rheumatoid arthritis (RA) and facilitates the migration of circulating immune cells into the inflamed joints. Recent studies have unveiled the complexity of this cascade, which involves intricate interactions between immune cells, neutrophil extracellular traps (NETs), reactive oxygen species (ROS), and inflammatory cytokines. Given the central role of the inflammatory cascade in RA pathogenesis, targeting it represents a highly promising therapeutic strategy. However, research specifically focused on modulating the inflammatory cascade remains limited. In this study, we introduce a novel bioinspired catalytic nanogel designed to target the inflammatory cascade for the immunotherapy of RA. Nanogel coated with cationic polymer enables the targeted penetration into cartilage as well as the capture of NETs via charge-trapping effects. The captured NETs are further degraded by DNase I-conjugating nanogel. To fundamentally reduce ROS that can induce NETs generation, nanogels exhibit intrinsic catalase, superoxide dismutase, and hydroxyl radical activities, effectively inhibiting oxidative stress responses. Of note, the enhanced therapeutic effects are observed in mouse RA model including targeted and long-term accumulation of cascade nanogel in the inflamed joints, efficient NETs scavenging, alleviated intra-articular inflammation, and reduced bone destruction. Also, transcriptome analysis indicates that nanogel treatment markedly downregulates NETs formation signaling pathway, upregulates anti-inflammatory pathways and finally reduces neutrophil infiltration-caused autoimmune damage. These results make the bioinspired catalytic nanogel system an ideal inflammatory cascades-targeting therapy for the systemic autoimmune disease.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"623"},"PeriodicalIF":12.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206535","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}