Materials Today Bio最新文献

{"title":"A nanozyme-augmented peripheral nerve-targeting liposome alleviates local immune inflammation and ferroptosis for enhanced facial nerve repair.","authors":"Qiang Zhou, Xiaolong Xu, Shuyi Lin, Yida Wang, Yuqi Han, Wenxin Liang, Ran Mo, Xianlong Wang, Yiyang Cheng, Chengxuan Tang, Lingxiao Zhang, Yiheng Yang, Xianzhen Chen, Liangle Liu","doi":"10.1016/j.mtbio.2026.103472","DOIUrl":"10.1016/j.mtbio.2026.103472","url":null,"abstract":"<p><p>Facial nerve injury (FNI) is a common form of peripheral nerve damage that often results in incomplete functional recovery due to a hostile microenvironment characterized by excessive oxidative stress and inflammatory activation. These pathological conditions disrupt Schwann cell homeostasis, impair myelin maintenance, and hinder nerve regeneration. Although ferroptosis, an iron-dependent lipid peroxidation-driven form of regulated cell death, has been implicated in peripheral nerve disorders, its involvement in acute FNI remains not fully defined. In this study, transcriptomic analysis of injured facial nerve tissue suggested ferroptosis-related transcriptional alterations and lipid peroxidation-associated cellular injury during the acute phase of FNI, including changes in ferroptosis-related gene expression, decreased GPX4 levels, and increased 4-HNE accumulation. To modulate this complex microenvironment, we developed a peripheral nerve-targeted, ROS-responsive liposomal nanoplatform (F-MHC@PNRLs) co-delivering Ferrostatin-1 (Fer-1) and Mn-doped CeO₂ nanozymes (MHC). The designed system integrates complementary mechanisms, where MHC provides catalytic ROS-scavenging activity to regulate upstream oxidative stress, while Fer-1 acts downstream to suppress lipid peroxidation propagation. In addition, NP41 peptide modification enhances peripheral nerve-associated retention and lesion-site accumulation following local administration. In a mouse FNI model, F-MHC@PNRLs effectively reduced oxidative stress, modulated macrophage polarization toward a reparative phenotype, and was associated with activation of NRF2/HO-1 antioxidant signaling while inhibiting NF-κB/MAPK-mediated inflammatory responses. Furthermore, F-MHC@PNRLs alleviated Schwann cell injury, preserved mitochondrial homeostasis, and promoted remyelination, leading to improved functional and electrophysiological recovery. Importantly, the formulation exhibited favorable preliminary biosafety in vivo. Collectively, these findings suggest that ferroptosis-related lipid peroxidation and oxidative inflammatory imbalance are involved in acute FNI pathology, and demonstrate that NP41-modified ROS-responsive liposomes co-delivering Fer-1 and Mn-doped CeO₂ nanozymes represent a promising strategy for enhancing facial nerve repair.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103472"},"PeriodicalIF":11.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xylem-inspired anisotropic porous silk microneedles enable efficient interstitial fluid sampling for local biomarker and proteomic profiling of skin diseases.","authors":"Jiahui Fu, Zhenni Chen, Xueyu Wen, Shaohua Li, Yi Wang, Zheyuan Li, Yingdi Zhu, Chenjie Xu, Hao Chang","doi":"10.1016/j.mtbio.2026.103480","DOIUrl":"10.1016/j.mtbio.2026.103480","url":null,"abstract":"<p><p>Chronic inflammatory skin diseases require safe and repeatable access to localized molecular information to enable mechanistic studies and precision management, yet existing sampling methods remain invasive or poorly representative of the skin microenvironment. Here, we develop xylem-inspired anisotropic porous silk microneedle (APSMNs)for rapid, high-yield, and minimally invasive sampling of skin interstitial fluid (ISF). By integrating directional cryo-templating, ice-templated solvent-exchange crosslinking, and Hofmeister effect-induced salting-out, APSMNs feature vertically aligned microchannels and high mechanical robustness, ensuring reliable skin penetration and swelling-independent ISF uptake. A single patch collects >10 μL ISF within 5 min, supports transport of macromolecules of at least 150 kDa, and achieves recovery efficiencies above 95%, yielding >180 μg total protein from mouse skin. In psoriasis-like mice, APSMN-collected ISF enables ELISA quantification of inflammatory biomarkers with sensitivity higher than serum and comparable to skin biopsy. Proteomic analysis identifies >6300 proteins in APSMN-collected ISF, exceeding serum and approaching skin biopsy, with significantly more upregulated proteins (2.89- and 2.54-fold increase compared with serum and biopsy, respectively). These findings demonstrate APSMNs as a robust platform for minimally invasive ISF sampling, enabling biomarker quantification and proteomic analysis. It supports longitudinal monitoring and discovery of disease-relevant molecular signatures in skin disorders.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103480"},"PeriodicalIF":11.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmable continuous gradient bioprinting for engineering spatially heterogeneous microenvironments.","authors":"Taekyung Choi, Hyungseok Lee","doi":"10.1016/j.mtbio.2026.103475","DOIUrl":"10.1016/j.mtbio.2026.103475","url":null,"abstract":"<p><p>Native tissues exhibit spatial heterogeneity in mechanical, cellular, and biochemical properties, yet reproducing such gradients in extrusion-based bioprinting remains challenging. Existing multi-material bioprinting approaches can create spatial variations in material composition, but often rely on discrete material transitions rather than continuous gradients. Here, we present a dual ball-valve mixing module that generates continuous gradients through real-time control of the mixing ratio between two precursor inks within a single-nozzle configuration. Complementary actuation of paired ball valves continuously adjusts the mixing ratio while maintaining constant extrusion conditions, transforming gradient formation into a programmable feature of the printing process. The versatility of the platform was demonstrated through gradients in mechanical stiffness, cell density, and biochemical cues. Continuous mixing enabled gradual transitions in material properties, reducing abrupt interfacial changes associated with discrete material deposition. Spatially defined cell-density distributions and graded two-population cellular interfaces were achieved while maintaining cell viability comparable to conventional extrusion bioprinting. Furthermore, a TGF-β1 gradient induced location-dependent epithelial-mesenchymal transition responses, demonstrating the ability to translate programmed biochemical gradients into spatially regulated cellular behavior. Consequently, this work establishes dynamic bioink mixing as an effective strategy for generating continuous and spatially programmable gradients, enabling the integration of material composition, cellular organization, and biochemical signaling within a single extrusion-based bioprinting process.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103475"},"PeriodicalIF":11.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Versatile metal-phenolic network structure (MPNs) as advanced delivery platforms for bioactive compounds: The design principles, foundations, applications, and future perspectives.","authors":"Yafei Zhang, Zenghui Xia, Yi Xue, Kai Zhang, Yujia Luo","doi":"10.1016/j.mtbio.2026.103477","DOIUrl":"10.1016/j.mtbio.2026.103477","url":null,"abstract":"<p><p>Despite possessing many important functions, the applications of bioactive compounds (BCs) are significantly limited due to various inherent shortcomings. In recent years, a novel class of materials known as metal-phenolic network structures (MPNs) has emerged. As the application scope of MPNs expands, it has become evident that this network structure can protect encapsulated active substances from adverse external environmental influences. This review first introduces the types and properties of polyphenols and metal ions, as well as the basis of their interactions. Subsequently, the construction methods of MPNs and their advantages as delivery platforms for BCs are discussed, including stimuli-responsive properties, adsorption properties, UV resistance, antioxidant activity, and antimicrobial effects. The mechanisms involved in the loading of BCs into MPNs and their novel applications in nanoparticles, films, coatings, capsules, emulsions, and hydrogels are elucidated. Additionally, the safety of MPNs and their fate within the human body are addressed. The role of artificial intelligence in advancing the development of MPNs as delivery platforms for BCs is also described in detail. Finally, the advantages, limitations, and obstacles to the clinical transformation of MPNs as delivery platforms are discussed. This review aims to uncover the significant role of MPNs in delivering BCs, thereby promoting the development of MPNs and the broader application of BCs.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103477"},"PeriodicalIF":11.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fe-MOF@Quercetin complex with light-controlled redox modulation for tumor wound repair.","authors":"Yuze Xu, Lan Chang, Zhaowenbin Zhang, Jiang Chang","doi":"10.1016/j.mtbio.2026.103484","DOIUrl":"10.1016/j.mtbio.2026.103484","url":null,"abstract":"<p><p>After the excision of tumor such as melanoma, the wound site often suffers from tumor recurrence and poor healing. A major clinical dilemma associated with photodynamic therapy is that the tumor excision site requires high reactive oxygen species (ROS) to inhibit tumor recurrence, while low ROS condition is required for promoting wound healing. To solve this problem, our study synthesized a MIL-101-(Fe)@Quercetin (MQ) complex material with oxygen vacancies and narrow bandgap characteristics, aiming to achieve light-controlled redox regulation of ROS generation. The structure of MQ enables it to efficiently separate holes (h⁺) and electron pairs (e^-) under laser irradiation, thereby generating ROS. At the same time, as a MOF- polyphenol complex, MQ exhibits excellent reducibility and biological activity, which can not only scavenge excess ROS after laser irradiation but also promote angiogenesis. <i>In vivo</i> experiments using mouse melanoma wound model demonstrate that MQ Microneedles (MQ@MNs), through light-controlled release of ROS in the tumor area, effectively inhibit tumor growth while scavenging ROS in the wound area to promote skin wound healing. In summary, this study provides new ideas and directions for the application of light-controlled redox regulation of ROS antioxidants in the treatment of melanoma wounds.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103484"},"PeriodicalIF":11.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic-metabolic coupling by SOX3/WDR5-SIRT5 signaling mediates the therapeutic effects of TGFβ-targeted exosomal nanoparticles in osteoarthritis.","authors":"Fu Qiwei, Shao Jiahua, Chen Shu, Cao Jia, Li Haobo, Zhu Jun","doi":"10.1016/j.mtbio.2026.103457","DOIUrl":"10.1016/j.mtbio.2026.103457","url":null,"abstract":"<p><p>The development of targeted nanotherapeutics capable of restoring chondrocyte homeostasis represents a major challenge in osteoarthritis (OA) treatment. In this study, we engineered a transforming growth factor-β (TGF-β) receptor-targeted exosome-nanoparticle hybrid system (TGFβ-Exo-NP) derived from chondrocytes and systematically evaluated its therapeutic efficacy and molecular mechanism. TGFβ-Exo-NP displayed uniform nanoscale morphology, favorable surface charge, and controlled release properties, with robust chondrocyte-specific uptake mediated by transforming growth factor-β receptor (TGF-βR) targeting. Functionally, TGFβ-Exo-NP markedly restored mitochondrial function, increased adenosine triphosphate (ATP) production, and inhibited apoptosis and pyroptosis in IL-1β-challenged chondrocytes, while promoting anabolic extracellular matrix synthesis. Integrated ChIP-seq, RNA-seq, and proteomic analyses demonstrated that TGFβ-Exo-NP activated a SOX3-driven epigenetic program involving histone H3 lysine 4 trimethylation (H3K4me3) enrichment and SIRT5 upregulation, thereby reprogramming mitochondrial metabolism. WDR5 was identified as a key exosomal effector protein required for chromatin activation and metabolic recovery. <i>In vivo</i>, TGFβ-Exo-NP significantly ameliorated cartilage destruction and subchondral bone remodeling in a destabilization of the medial meniscus (DMM) rat model, with improved gait performance and histological outcomes. These results establish a multifunctional exosome-based nanosystem as a precision therapeutic strategy and provide mechanistic insights into epigenetic-metabolic reprogramming in OA.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103457"},"PeriodicalIF":11.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering adaptive self-healing biomaterials from jammed microfluidic elastomeric particles.","authors":"Jennifer Kieda, Kaitlyn Ramsay, Richard Jiang, Shira Landau, Ramak Khosravi, Chuan Liu, Amid Shakeri, Karl T Wagner, Dhana Abdo, Anna Maria Popovic, Sean Farley, Katherine S Elvira, Milica Radisic","doi":"10.1016/j.mtbio.2026.103473","DOIUrl":"10.1016/j.mtbio.2026.103473","url":null,"abstract":"<p><p>Biomaterials designed for implantation must accommodate the dynamic mechanical and structural environment of the human body. Yet, current strategies for creating materials capable of adapting their shape post-implantation remain limited. In this work, we introduced a remoldable, biodegradable, and biocompatible granular scaffold composed of monodisperse poly(octamethylene maleate (anhydride) citrate) (POMaC) particles. Monodisperse POMaC droplets with controlled diameters were generated using a droplet microfluidic platform, then subsequently jammed and UV-crosslinked to form interconnected, porous, and self-healing elastomeric scaffolds. The scaffold chemical composition and crosslinking parameters directly influenced mechanical properties, stability, and permeability, enabling tunability across a range of tissue engineering applications. The granular scaffold exhibited autonomous self-healing, enhanced molecular diffusivity, and robust cell infiltration, while remaining moldable into prescribed geometries under both <i>in vitro</i> and <i>in vivo</i> conditions. Notably, following implantation, the granular scaffolds could be remolded <i>in vivo</i> 24 h post-implantation, allowing adaptation to a desired geometry while preserving structural integrity, promoting the recruitment of pro-reparative macrophages, and facilitating vascular ingrowth. Collectively, this work established a versatile strategy for designing adaptive implantable biomaterials capable of responding to the body's dynamic environment, with broad potential applications in regenerative medicine and tissue engineering.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103473"},"PeriodicalIF":11.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target FADS1-arachidonic acid-ferroptosis axis: A metabolic bridge linking matrix stiffness to PDAC stemness.","authors":"Tiancheng Gong, Jiashuai Yan, Hongyu Zhu, Xiaoqi Guan, Haowei Xing, Zhen Wang, Di Wu, Biwen Zhu, Xue Zhang, Yidan Ma","doi":"10.1016/j.mtbio.2026.103455","DOIUrl":"10.1016/j.mtbio.2026.103455","url":null,"abstract":"<p><p>The elevated stiffness of extracellular matrix (ECM), one of the typical physical hallmarks of pancreatic ductal adenocarcinoma (PDAC), which was proved to promote stemness and leads to adverse prognosis. Therefore, to dissect the underlying mechanisms between matrix stiffness and stemness is important. To this end, stiffness tunable hydrogel based on polyacrylamide (PA) was employed to simulate the stiffness of PDAC microenvironment. Our results illustrated that stiff matrix enhanced PDAC (MIA PaCa-2 and PANC-1 cells) stemness by inhibiting ferroptosis. Lipidomic analyses further revealed that matrix stiffness reprogrammed medium and long chain fatty acid metabolism, with particularly prominent arachidonic acid (AA) depletion. Intriguingly, AA supplementation restored ferroptosis sensitivity and reversed stiffness-induced stemness enhancement. Mechanistically, matrix stiffness inhibits AA content by downregulating FADS1 (fatty acid desaturase 1), a key biosynthesis enzyme. Simultaneously, the ferroptosis was suppressed accompanied by the AA reduction, which was validated via decreased lipid peroxidation and preserved mitochondrial morphology. Besides, FADS1 knockdown recapitulated the stiff matrix effects, causing ferroptosis inhibition and stemness enhancement, which could be rescued by AA supplementation. Collectively, our data shed light on the novel mechanism: matrix stiffness-suppressed FADS1 drives AA-replied ferroptosis inhibition, ultimately promoting PDAC stemness. Targeting the FADS1-AA-ferroptosis axis may provide practicable opportunities for the therapy of PDAC.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103455"},"PeriodicalIF":11.0,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatically triggered glucose-releasing scaffolds as nutritional supports for millimeter-scale tissue engineering.","authors":"Panitporn Laowpanitchakorn, Marie Piantino, Tomoya Matsuo, Michiya Matsusaki","doi":"10.1016/j.mtbio.2026.103474","DOIUrl":"10.1016/j.mtbio.2026.103474","url":null,"abstract":"<p><p>Construction of millimeter-sized tissues to mimic real human tissue or organ is still challenging, as oxygen and nutrients have a diffusion limit of only 100-200 μm from blood vessels. Almost all mammalian cells except red blood cells and platelets need a glucose supply to support their metabolic activities and functions. Inspired by the properties of blood vessels, we developed an alginate scaffold that is capable to release glucose by hydrolysis of glycogen via enzymes such as amyloglucosidase in this study. The scaffold can be flexibly shaped into glucose-releasing capsules (Glc-RCs) and glucose-releasing fibers (Glc-RFs). It was demonstrated that Glc-RCs can provide sustained release of glucose for up to 4 days and have no negative effect on C2C12 mouse myoblast cell and human adipose-derived mesenchymal stem cell proliferation. Glc-RCs could also support differentiation of C2C12 into myotubes after 7 days of application without the need for media replenishment. Glc-RFs were incorporated into millimeter-scale 3D tissue-engineered constructs, where they reduced the apoptotic activity of normal human dermal fibroblasts (NHDFs) located within approximately 1000 μm from the fibers. In particular, the relationship between glucose diffusion distance and resulting cellular responses like apoptosis has not previously been documented in other glucose-releasing material studies. Thus, the developed glucose-releasing scaffold has the potential to be shaped into different sizes by 3D extrusion printing to serve as a localized glucose delivery system to further study glucose diffusion profiles as well as supplying glucose for supporting mm-sized tissue construction.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103474"},"PeriodicalIF":11.0,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface charge engineering shields extracellular vesicles from plasma protein corona to enable systemic extrahepatic targeting.","authors":"Taotao Tang, Mengyun Wang, Xiaowei Xu, Jin Wang, Yan Wang, Fangzhou Wang, Deping Wu, Yilin Zhang, Shuangshuang Liu, Lingting Kong, Zhiqing Chen, Feng Chen, Yi Wen, Bin Wang, Junjia Wang, Bicheng Liu, Linli Lv","doi":"10.1016/j.mtbio.2026.103471","DOIUrl":"10.1016/j.mtbio.2026.103471","url":null,"abstract":"<p><p>The plasma protein corona (PC) critically influences the <i>in vivo</i> fate of nanomedicines, yet its composition and impact on extracellular vesicles (EVs) remain poorly defined. Using a biomimetic circulation system, we characterized PC formation and modulation on two clinically relevant EV types: mesenchymal stromal cell-derived EVs (MSC-EVs) and HEK293F-derived EVs (293F-EVs). Under dynamic flow, both EV types acquired stable coronas, resulting in increased particle size and decreased surface charge. Proteomic profiling revealed a shared corona signature enriched in immunoglobulins, complements, and other plasma components. Functionally, PC formation enhanced macrophage uptake and triggered inflammatory activation, primarily via interactions between corona-bound immunoglobulins or complement C3 and their respective receptors. To disrupt this process, we developed a charge-shielding strategy using positively charged chitosan oligosaccharide (COS) to inhibit PC assembly. COS coating effectively neutralized EV surface charge and reduced opsonin adsorption and non-specific macrophage clearance, thereby reshaping EV biodistribution-limiting hepatic sequestration and enhancing delivery to extrahepatic organs. In a murine sepsis model, COS-modified MSC-EVs further improved renal and pulmonary outcomes and markedly increased survival. Collectively, these findings elucidate the molecular architecture and immunological impact of the EV-associated plasma PC and introduce a promising anti-corona strategy for engineering stealthier and more effective EV-based nanotherapeutics.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103471"},"PeriodicalIF":11.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}