Biomaterials最新文献_第8页

Bridging acute-chronic myocardial infarction treatment: Dual-regulating of ROS/fibrosis via microenvironment-responsive release of NO and curcumin 桥接急慢性心肌梗死治疗：通过微环境响应性释放NO和姜黄素对ROS/纤维化的双重调节

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123954

Fang Zhang , Bingbing Zhao , Keqiang Lu , Xueping Zeng , Zikun Wang , Wei Chen , Yunyun Zhou , Juanjuan Peng , Lingzhi Zhao

{"title":"Bridging acute-chronic myocardial infarction treatment: Dual-regulating of ROS/fibrosis via microenvironment-responsive release of NO and curcumin","authors":"Fang Zhang , Bingbing Zhao , Keqiang Lu , Xueping Zeng , Zikun Wang , Wei Chen , Yunyun Zhou , Juanjuan Peng , Lingzhi Zhao","doi":"10.1016/j.biomaterials.2025.123954","DOIUrl":"10.1016/j.biomaterials.2025.123954","url":null,"abstract":"<div><div>Oxidative stress and fibrosis are core drivers of post-myocardial infarction dysfunction. Conventional therapies predominantly address either acute oxidative damage or chronic fibrosis, lacking strategies that concurrently target the two interconnected processes. Here, a microenvironment-responsive nanomedicine delivering nitric oxide (NO) and curcumin specifically to the infarcted heart is presented (named C@Si-NM). Constructed from glutathione-sensitive cyclic nitrate-trimethylene carbonate-polyethylene glycol block copolymer micelles crosslinked with silica, the system releases both NO and the encapsulated curcumin upon encountering elevated glutathione levels at the infarction site. In cardiomyocytes, NO suppresses the opening of mitochondrial permeability transition pore, inhibiting the release of reactive oxygen species, while curcumin directly acts as an antioxidant. In fibroblasts, NO inhibits the TGF-β/Smad pathway and curcumin downregulates the production of TGF-β, jointly suppressing fibrosis. The combined nanomedicine C@Si-NM significantly improved cardiac function in a rat model of MI after four weeks of treatment, resulting in an ejection fraction of 74 %. This value approached the normal range of 81 % and was superior to the outcomes observed with NO monotherapy at 62 % or curcumin monotherapy at 63 %. This strategy effectively mitigates both oxidative damage and fibrosis, bridging the gap between acute and chronic therapeutic interventions of myocardial infarction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123954"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomimetic and microenvironment-adaptive nanoplatform potentiates photodynamic therapy of rheumatoid arthritis via H2S-Modulated oxygen metabolism 仿生和微环境适应性纳米平台通过h2s调节氧代谢增强类风湿关节炎的光动力治疗

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-15 DOI: 10.1016/j.biomaterials.2025.123926

Xican Zhang , Shiyu Meng , Yi Xiao , Yonghang Liu , Zhuang Tang , Ao Li , Kefan Wu , Chong Cheng , Zhengwei Mao , Hui Guo , Yi Zhun Zhu , Xiaolin Wang

{"title":"Biomimetic and microenvironment-adaptive nanoplatform potentiates photodynamic therapy of rheumatoid arthritis via H2S-Modulated oxygen metabolism","authors":"Xican Zhang , Shiyu Meng , Yi Xiao , Yonghang Liu , Zhuang Tang , Ao Li , Kefan Wu , Chong Cheng , Zhengwei Mao , Hui Guo , Yi Zhun Zhu , Xiaolin Wang","doi":"10.1016/j.biomaterials.2025.123926","DOIUrl":"10.1016/j.biomaterials.2025.123926","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) enables the selective eradication of inflamed synovium to reverse joint destruction in rheumatoid arthritis (RA). Nonetheless, the synovial hypoxia and poor photosensitizer biodistribution in the arthritic joints profoundly restrain the clinical application of PDT. Herein, we constructed a multipronged nanosystem (MM@SC-HN) through hierarchical integration of macrophage membrane (MM) coating and hydrogen sulfide (H<sub>2</sub>S) donor (<em>S</em>-propargyl-cysteine, SPRC)/photosensitizer (Chlorine 6, Ce6) co-conjugated hyaluronic acid nanogels (SC–HN) for potentiated PDT of RA. Interestingly, MM@SC-HN demonstrated preferential accumulation in the inflamed joints rather than in the major organs due to the intrinsic inflammation chemotactic capacity of the MM cloak. Moreover, SPRC undergoes pH-triggered liberation in synovial fluid to generate therapeutic H<sub>2</sub>S, simultaneously alleviating hypoxia and amplifying Ce6-mediated PDT efficacy through mitochondrial respiration modulation. Consequently, MM@SC-HN profoundly reshaped the intricate joint microenvironment featured by inflammation, hypoxia, pannus formation, hyperplasia, and oxidative stress, which ultimately led to ameliorated paw swelling, diminished inflammation score, and enhanced joint repair in adjuvant-induced arthritis rats. In addition, MM@SC-HN exhibited desirable hemo/cyto/histological compatibility that favored clinical translation. Collectively, our study provides a smart nanoplatform for clinical RA treatment and represents a novel approach for reinforced PDT that is readily adaptable to various diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123926"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I 从免疫复合体中剥离无细胞DNA对于使用DNA酶I控制炎症至关重要。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2026-01-06 DOI: 10.1016/j.biomaterials.2026.123992

Shi Chen , Yibo Du , Chenxu Zhu , Chuang Li , Xingliang Liu , Lixin Liu , Yongming Chen

{"title":"Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I","authors":"Shi Chen , Yibo Du , Chenxu Zhu , Chuang Li , Xingliang Liu , Lixin Liu , Yongming Chen","doi":"10.1016/j.biomaterials.2026.123992","DOIUrl":"10.1016/j.biomaterials.2026.123992","url":null,"abstract":"<div><div>Excessive accumulation of cell-free DNA (cfDNA) has been identified as a primary pathogenic factor in autoimmune diseases. The circulating deoxyribonuclease (DNase) maintaining cfDNA homeostasis is suppressed, and thus exogenous DNase has been applied to degrade cfDNA for inflammation control. However, in pathological states, cfDNA and cationic endogenous peptide (<em>e.g.</em>, LL37) form immune complexes (ICs), which not only weaken DNase efficacy but also facilitate immune cell internalization to induce an inflammatory response. With LL37-DNA as a model IC, here we found that the LL37 occupancy not only sterically hinders cfDNA's access to the catalytic sites but also induces deactivation of DNase <em>via</em> formation of ternary complexes (LL37-DNA-DNase I). This transition critically impairs the activity of DNase I within LL37-rich inflammatory microenvironments. Thus, we postulated that heparin, a clinically approved anionic glycosaminoglycan, could destruct the ICs and liberate cfDNAs, restoring their susceptibility to degradation. Indeed, we found that a combination of heparin and DNase I facilitates the DNA degradation and inhibits the ICs-mediated TLR9 activation <em>in vitro</em>. However, the therapeutic outcome observed in rheumatoid arthritis (RA) model was still suboptimal, attributed to the short plasma half-life of DNase. To validate this, we engineered a DNase nanoparticle (DNase@TANP) capable of sustained release of the enzyme. Consequently, the sequential administration of heparin and DNase@TANP (with a 30-min interval) to RA model demonstrated a synergistic cfDNA degradation efficiency, effectively suppressing Toll-like receptor (TLR) mediated inflammatory pathways and ameliorating joint inflammation. This strategy, leveraging clinically approved agents for cfDNA clearance, establishes a promising therapeutic paradigm for cfDNA-associated autoimmune disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123992"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to ‘Enzyme-induced in vivo assembly of gold nanoparticles for imaging-guided synergistic chemo-photothermal therapy of tumor’ [Biomaterials 223 (2019) 119460] “酶诱导的金纳米颗粒在体内组装用于成像引导的肿瘤协同化学光热治疗”的更正[生物材料223(2019)119460]。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2026-01-17 DOI: 10.1016/j.biomaterials.2025.123971

Kuikun Yang , Yijing Liu , Yin Wang , Qilong Ren , Hongyu Guo , John B. Matson , Xiaoyuan Chen , Zhihong Nie

引用次数: 0

Charge-based supramolecular peptide nanocomplexes for oral delivery via transporter-driven endocytosis 通过转运蛋白驱动的内吞作用口服递送的基于电荷的超分子肽纳米复合物

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123903

So-Hyeon Park , Gaeun Ma , Seong Jin Park , Seong-Bin Yang , Minho Seo , Jun-Hyuck Lee , Seho Kweon , Jooho Park

{"title":"Charge-based supramolecular peptide nanocomplexes for oral delivery via transporter-driven endocytosis","authors":"So-Hyeon Park , Gaeun Ma , Seong Jin Park , Seong-Bin Yang , Minho Seo , Jun-Hyuck Lee , Seho Kweon , Jooho Park","doi":"10.1016/j.biomaterials.2025.123903","DOIUrl":"10.1016/j.biomaterials.2025.123903","url":null,"abstract":"<div><div>The development of charge-based self-assembled supramolecules can provide a groundbreaking advancement in the oral delivery of nanoparticles. In this study, we developed a series of positively charged peptide-engineered bile acids (PCBs) for the first time to interact with the negatively charged semaglutide (SG), a widely used Glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of obesity and diabetes. Among the synthesized PCBs, PCB<sub>4</sub> self-assembled with semaglutide via electrostatic interactions to form stable supramolecular nanoparticles, termed positively charged bile acid-saturated semaglutide (PBSG) nanocomplexes, with an average size of approximately 279 nm under aqueous conditions. These PBSG nanocomplexes demonstrated enhanced permeability and absorption through bile acid transporter-driven endocytosis in intestinal cells and tissues, inducing natural breakdown of cell membranes. Notably, PBSG nanocomplex increased the gastrointestinal (GI) permeation and oral absorption of semaglutide, improved therapeutic efficacy in a high-fat diet (HFD)-induced animal model, and inhibited bile acid transporter activity. Moreover, Oral PBSG nanocomplex treatment elevated GLP-1 expression <em>in vivo</em> by facilitating semaglutide delivery and modulating bile acid metabolism at the same time. The development of these novel, charge-based, self-assembling oral peptide nanocomplexes, leveraging positively charged bile acids and transporter-driven uptake, represents a significant advancement in oral nanoparticle delivery and the design of therapeutic nanomaterials.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123903"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual-targeting nuclear and mitochondrial DNA damage drives immunogenic activation via PANoptosis for synergistic magneto-thermodynamic-chemotherapy 双靶向核和线粒体DNA损伤通过PANoptosis驱动免疫原性激活，用于协同磁热化疗

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-15 DOI: 10.1016/j.biomaterials.2025.123924

Lingcheng Wu , Jiaxin Su , Youde Cao , Hui Yuan , Zuying Li , Jingwen Ren , Mingzhao Xiao , Kexiao Yu , Bing Liang

{"title":"Dual-targeting nuclear and mitochondrial DNA damage drives immunogenic activation via PANoptosis for synergistic magneto-thermodynamic-chemotherapy","authors":"Lingcheng Wu , Jiaxin Su , Youde Cao , Hui Yuan , Zuying Li , Jingwen Ren , Mingzhao Xiao , Kexiao Yu , Bing Liang","doi":"10.1016/j.biomaterials.2025.123924","DOIUrl":"10.1016/j.biomaterials.2025.123924","url":null,"abstract":"<div><div>Solid tumors often evade immunotherapy due to poor drug penetration, insufficient radical accumulation, and low immunogenicity. To address this, we engineer an injectable liquid-solid phase-transition implant (Fe<sub>3</sub>O<sub>4</sub>/AIPH/DDP@PLGA) that mimics an “AIM2 agonist” to trigger nuclear/mitochondrial DNA dual-damage and PANoptosis for enhanced magneto-thermal dynamic immunotherapy. The gel exhibits exceptional injectability, shape adaptability, and localized retention, enabling precise intratumoral delivery while minimizing systemic toxicity. Under alternating magnetic fields (AMF), the Fe<sub>3</sub>O<sub>4</sub> component generates magnetothermal effects, triggering azo bond cleavage in AIPH for controlled •C radical release and Fe<sup>2+</sup>-mediated Fenton reactions with tumor-overexpressed H<sub>2</sub>O<sub>2</sub>. In cancer therapy, cisplatin not only amplifies ROS-induced DNA damage but also, as a widely utilized chemotherapeutic agent, induces nuclear DNA (nDNA) lesions via interstrand/intrastrand crosslinking with DNA and disruption of repair mechanisms. Cytosolic dsDNA accumulation activates AIM2-PANoptosome assembly, initiating PANoptosis, engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis), that eradicates primary tumors and primes systemic immunity through dendritic cell activation and CD8<sup>+</sup> T-cell recruitment. This dual-damage strategy overcomes penetration barriers and immunogenic “cold” tumor limitations, achieving robust anti-tumor efficacy in prostate cancer models. Our work not only deciphers the mechanistic interplay of Fe<sub>3</sub>O<sub>4</sub>/AIPH/DDP@PLGA as a biomimetic AIM2 activator but also pioneers a transformative paradigm for solid tumor immunotherapy through controlled radical amplification and PANoptosis induction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123924"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteoimmunometabolic modulation via hydrogen-self-supplying magnesium-reinforced collagen membrane for enhanced guided bone regeneration 通过氢自供镁增强胶原膜促进骨再生的骨免疫代谢调节。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-19 DOI: 10.1016/j.biomaterials.2025.123928

Yuqing Mu , Zhibin Du , Wendong Gao , Ze He , Lan Xiao , Yinghong Zhou , Imaan Ahmed , Huan Dai , Ming Liu , Jiaying Liu , Xin Wang , Sheng Yu , Yin Xiao

{"title":"Osteoimmunometabolic modulation via hydrogen-self-supplying magnesium-reinforced collagen membrane for enhanced guided bone regeneration","authors":"Yuqing Mu , Zhibin Du , Wendong Gao , Ze He , Lan Xiao , Yinghong Zhou , Imaan Ahmed , Huan Dai , Ming Liu , Jiaying Liu , Xin Wang , Sheng Yu , Yin Xiao","doi":"10.1016/j.biomaterials.2025.123928","DOIUrl":"10.1016/j.biomaterials.2025.123928","url":null,"abstract":"<div><div>Localized delivery of molecular hydrogen (H<sub>2</sub>) in bone tissue engineering remains largely unexplored, despite its potent antioxidative and anti-inflammatory properties. In this study, we present a multifunctional collagen membrane reinforced with micro-magnesium wires coated with metal-phenolic networks (Col-MMW), designed for guided bone regeneration (GBR). The embedded magnesium wires provide mechanical reinforcement, enhancing the membrane's structural integrity and space-maintaining capability during early healing. Concurrently, magnesium degradation enables sustained, site-specific release of H<sub>2</sub> and magnesium ions (Mg<sup>2+</sup>), offering a synergistic strategy to modulate the osteoimmune environment. Col-MMW attenuates intracellular reactive oxygen species (ROS) and reprograms cellular metabolism from glycolysis toward oxidative phosphorylation, thereby activating the nuclear factor erythroid 2-related factor 2 (NRF-2)-mediated redox balance pathway and suppressing nuclear factor kappa B (NF-κB) pathway-driven inflammation. This osteoimmunometabolic reprogramming leads to a significant reduction in inflammatory responses. <em>In vivo</em> studies, including rat subcutaneous implantation and calvarial defect models, demonstrated that the immunoregulatory effects of Col-MMW significantly promoted osteogenesis. By integrating mechanical reinforcement with localized metabolic and immune modulation, Col-MMW redefines the design paradigm of GBR membranes. These findings highlight Col-MMW as a next-generation biomaterial that combines structural integrity with targeted osteoimmunomodulation, addressing the unmet need for intelligent biomaterials for bone repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123928"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatiotemporal controlled disintegration enabling injected magnetic hydrogel for percutaneous hepatocellular carcinoma treatment 经皮肝细胞癌的时空可控崩解注射磁性水凝胶治疗

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-26 DOI: 10.1016/j.biomaterials.2025.123952

Bing Chen , Hanye Xing , Xingyu Liu , Jinlong Hu , Liang Dong , Xu Yan , Yonghong Song , Yang Lu

{"title":"Spatiotemporal controlled disintegration enabling injected magnetic hydrogel for percutaneous hepatocellular carcinoma treatment","authors":"Bing Chen , Hanye Xing , Xingyu Liu , Jinlong Hu , Liang Dong , Xu Yan , Yonghong Song , Yang Lu","doi":"10.1016/j.biomaterials.2025.123952","DOIUrl":"10.1016/j.biomaterials.2025.123952","url":null,"abstract":"<div><div>Disintegrating hydrogels offer the advantages of synergistically enhancing therapeutic efficacy in locoregional percutaneous treatment for early hepatocellular carcinoma, enabling on-demand drug delivery with reduced side effects. However, current disintegration processes suffer from limited precise control and weak tissue penetration. Herein, we constructed an injectable ferrimagnetic hydrogen bonding cross-linked hydrogel (named as FPH) as a locoregional percutaneous agent by integrating ferrimagnetic nanoparticles into a polyvinyl alcohol (PVA) crosslinked network. This hydrogel enables remote magnetothermally triggered disintegration under an alternating magnetic field (AMF), with its disintegration temperature precisely tunable by adjusting the hydrogel's solid content. Under magnetic heating effect, FPH achieved remote “gel to disintegration” behavior at a desired temperature range of around 47 °C, effectively suppressing tumor cells and minimizing harm to normal tissues. By contrast, other commonly used hydrogen-bonded network of gelatin hydrogel disintegrated below body temperature or agarose hydrogel disintegrated over 70 °C. Benefiting from magnetothermal-controlled disintegration, drug-loaded FPH exhibited an increased release efficiency from ∼8 % (without AMF) to ∼45 % (with AMF) within 1 h. Following ultrasound-guided percutaneous delivery, FPH<sub>DOX</sub> exhibited synergistic efficacy with magnetic hyperthermia and disintegration-mediated chemotherapy in rabbit liver tumors. Additionally, FPH is fabricated using clinically approved pharmaceutical excipients, ensuring excellent biocompatibility. This strategy inspires the design of spatiotemporally controllable disintegrating hydrogels with limitless tissue penetration depth, and expands their potential in percutaneous hepatocellular carcinoma treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123952"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrasound-responsive renal-targeted nanoparticles deliver TAK-242 to inhibit NF-κB/NLRP3 signaling and attenuate sepsis-associated acute kidney injury 超声应答肾靶向纳米颗粒递送TAK-242抑制NF-κB/NLRP3信号，减轻脓毒症相关的急性肾损伤

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-14 DOI: 10.1016/j.biomaterials.2025.123922

Yingnan Guo , Ying Wang , Baoquan Wang , Shuang Peng , Na Li , Dan Zhang , Huiping Wu

{"title":"Ultrasound-responsive renal-targeted nanoparticles deliver TAK-242 to inhibit NF-κB/NLRP3 signaling and attenuate sepsis-associated acute kidney injury","authors":"Yingnan Guo , Ying Wang , Baoquan Wang , Shuang Peng , Na Li , Dan Zhang , Huiping Wu","doi":"10.1016/j.biomaterials.2025.123922","DOIUrl":"10.1016/j.biomaterials.2025.123922","url":null,"abstract":"<div><div>Sepsis-associated acute kidney injury (SA-AKI) remains a major clinical challenge due to the lack of effective targeted therapies. In this study, we designed ultrasound-responsive, renal-targeted nanoparticles based on serine-modified liposomes co-loaded with the TLR4 inhibitor TAK-242 and perfluoropentane (LIPs-S@TAK/PFP). The nanoplatform enables controlled TAK-242 release under low-intensity focused ultrasound through ultrasound-targeted microbubble destruction, providing both therapeutic delivery and real-time imaging capability. <em>In vitro</em> studies using HK-2 cells demonstrated that the nanoparticles effectively downregulated TLR4, reduced NF-κB activation, suppressed pro-inflammatory cytokine secretion (TNF-α, IL-1β, IL-6), decreased reactive oxygen species (ROS) generation, and attenuated pyroptosis. In septic rat models, LIPs-S@TAK/PFP significantly improved renal function, as evidenced by reduced serum creatinine, blood urea nitrogen, and cystatin-C levels, while alleviating tubular injury. Histological and molecular analyses further revealed inhibition of NLRP3 inflammasome activation and pyroptotic markers, including Caspase-1 and GSDMD-N. Multi-omics profiling confirmed that treatment predominantly suppressed the TLR4/NF-κB/NLRP3 axis while enhancing antioxidant defense, reflected by increased superoxide dismutase and reduced malondialdehyde. Collectively, these findings demonstrate that ultrasound-responsive LIPs-S@TAK/PFP nanoparticles provide efficient renal-targeted delivery of TAK-242, mitigate inflammation and pyroptosis, and protect kidney function in SA-AKI. This strategy highlights a promising nanomedicine-based therapeutic approach for sepsis-induced organ injury.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123922"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering fluorescent iNOS-Inhibitory covalent organic frameworks: Fewer doses than fluticasone propionate for house dust mite-induced allergic rhinitis treatment 工程荧光inos -抑制共价有机框架：比丙酸氟替卡松治疗屋尘螨引起的变应性鼻炎的剂量更少

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-23 DOI: 10.1016/j.biomaterials.2025.123946

Shu-Jia Sang , Jia-Lu Zhuang , Xi-Xi Chen , Wen-Long Huang , Zhong-Lian Wang , Ji Lu , Mao-Yu Jiang , Yu-Chen Liu , Qin Wang , Guiyang Zhang , Ye-Hai Liu

{"title":"Engineering fluorescent iNOS-Inhibitory covalent organic frameworks: Fewer doses than fluticasone propionate for house dust mite-induced allergic rhinitis treatment","authors":"Shu-Jia Sang , Jia-Lu Zhuang , Xi-Xi Chen , Wen-Long Huang , Zhong-Lian Wang , Ji Lu , Mao-Yu Jiang , Yu-Chen Liu , Qin Wang , Guiyang Zhang , Ye-Hai Liu","doi":"10.1016/j.biomaterials.2025.123946","DOIUrl":"10.1016/j.biomaterials.2025.123946","url":null,"abstract":"<div><div>Allergic rhinitis (AR) is a chronic inflammatory disease primarily mediated by T<sub>H</sub>2-type immune responses, which is clinically managed with glucocorticoid therapy. However, this approach is limited by its variable efficacy and notable side effects. Herein, we developed two covalent organic framework (COF) nanoflakes—Aming-COF and Aming-BCOF—with inducible nitric oxide synthase (iNOS) inhibitory functions. We achieved targeted delivery and <em>in vivo</em> tracing by polymerizing the iNOS inhibitor aminoguanidine with a tetraphenylethylene fluorescent group through covalent bonds. In a mouse AR model induced by house dust mites, intranasal administration of Aming-COF demonstrated therapeutic efficacy: inhibiting excessive iNOS expression in the nasal mucosa to alleviate oxidative stress damage; repairing tight junction proteins such as ZO-1 and occludin to enhance epithelial barrier function; and regulating GATA-3/T-bet expression to rebalance T<sub>H</sub>1/T<sub>H</sub>2 immunity, thereby reducing T<sub>H</sub>2-type cytokines such as IL-4 and IL-5 while increasing T<sub>H</sub>1-type IFN-γ levels. Transcriptome analysis revealed its mechanism of action: inhibition of the IL5Rα-JAK-STAT signaling pathway. Aming-COF showed greater efficacy than fluticasone propionate with fewer doses (3 <em>vs.</em> 5) and no significant hepatotoxicity or nephrotoxicity, indicating good biosafety. This study provides a novel nanomaterial strategy for AR precision therapy and opens new directions for the application of COFs in immune regulation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123946"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0