Bioactive Materials最新文献_第9页

ROS-scavenging nanoparticles loaded with tectorigenin protect against acetaminophen-induced hepatotoxicity by interrupting the calcium/ROS-mediated pathogenic endoplasmic reticulum–Mitochondrial signaling cascade 负载紫丁香黄素的活性氧清除纳米颗粒通过阻断钙/活性氧介导的致病性内质网-线粒体信号级联来保护对乙酰氨基酚诱导的肝毒性

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-13 DOI: 10.1016/j.bioactmat.2025.12.016

Yaqi Zhang , Zeyuan Jin , Lvwan Xu , Zilong Zhong , Xinyu Wang , Changyou Gao , Lanjuan Li

Acetaminophen (APAP) overdose is a leading cause of acute liver injury (ALI) and acute liver failure (ALF) worldwide, representing a major clinical and public health challenge due to its rapid onset and high morbidity. Current clinical treatment is limited to N-acetylcysteine (NAC), but its efficacy is highly time-dependent and the prolonged regimen imposes additional clinical burdens and side effects. Natural compounds hold tremendous promise for hepatoprotection, but their clinical translation is limited by unfavorable physicochemical and pharmacokinetic properties. In this study, tectorigenin (Tec), an isoflavone possessing anti-inflammatory and antioxidative activity, was encapsulated within a reactive oxygen species (ROS)-responsive nanoplatform (PBHB@Tec) to enhance bioavailability and enable site-selective hepatoprotection. PBHB@Tec possessed diameters compatible with passage through hepatic sinusoidal fenestrae into the space of Disse enabling direct hepatocyte interaction, while exhibiting potent ROS scavenging activity and undergoing ROS-triggered morphological degradation that accelerated Tec release under oxidative conditions. In an APAP-induced ALI mouse model, PBHB@Tec markedly attenuated ALI phenotypes. Mechanistically, PBHB@Tec reduced endoplasmic reticulum (ER) stress, which alleviated ER Ca²⁺ leak and subsequently prevented mitochondrial Ca²⁺ overload. This, in turn, lowered mitochondrial ROS production and restored antioxidant defenses, collectively disrupting the feedforward calcium/ROS apoptotic cascade. These broad improvements in ER-mitochondrial homeostasis positioning PBHB@Tec as a promising ROS-responsive nanotherapy for APAP-induced hepatotoxicity.

对乙酰氨基酚（APAP）过量是世界范围内急性肝损伤（ALI）和急性肝衰竭（ALF）的主要原因，由于其快速发作和高发病率，代表了一个重大的临床和公共卫生挑战。目前的临床治疗仅限于n -乙酰半胱氨酸（NAC），但其疗效具有高度的时间依赖性，延长治疗方案会带来额外的临床负担和副作用。天然化合物在保护肝脏方面具有巨大的前景，但它们的临床转化受到不利的物理化学和药代动力学性质的限制。在这项研究中，tectorigenin (Tec)，一种具有抗炎和抗氧化活性的异黄酮，被封装在活性氧（ROS）响应的纳米平台（PBHB@Tec）中，以提高生物利用度并实现位点选择性肝保护。PBHB@Tec具有与通过肝窦窗进入Disse空间相容的直径，能够直接与肝细胞相互作用，同时表现出强大的ROS清除活性，并经历ROS触发的形态降解，加速氧化条件下Tec的释放。在apap诱导的ALI小鼠模型中，PBHB@Tec显著减弱了ALI表型。在机制上，PBHB@Tec降低内质网（ER）应激，从而减轻ER Ca2+泄漏，随后防止线粒体Ca2+过载。这反过来又降低了线粒体ROS的产生并恢复了抗氧化防御，共同破坏了前馈钙/ROS凋亡级联。这些er线粒体稳态的广泛改善使PBHB@Tec成为一种有希望的ros反应性纳米疗法，用于apap诱导的肝毒性。

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引用次数: 0

Modular nanotherapeutics with spatiotemporal precision for phase-specific treatment of intracerebral hemorrhage 具有时空精度的模块化纳米疗法用于脑出血的阶段性治疗

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-12 DOI: 10.1016/j.bioactmat.2025.12.007

Wanli Yu , Zhiyu Chen , Bo Wu , Chunfan Zhang , Ying Han , Dewei Zou , Jianxiang Zhang , Nan Wu

Intracerebral hemorrhage (ICH) is a life-threatening neurological disorder characterized by spatiotemporally evolving pathological cascades, necessitating interventions that dynamically adapt to its multiphasic injury progression. Here, we report modular polymer (PPP)-based nanotherapeutics engineered for stage-specific therapy of ICH through sequential pharmacological actions. The PPP architecture integrates a hydrophilic segment and a hydrophobic, reactive oxygen species (ROS)-responsive motif onto a polyamine scaffold, enabling ROS-triggered programmed dissociation, on-demand anti-inflammatory agent release, and iron chelation. This design confers spatiotemporal therapeutic precision: during the hyperacute phase, PPP nanoparticles promote rapid hemostasis and efficiently scavenge cell-free DNA (cfDNA); in the acute phase, they attenuate neuroinflammation through ROS-mediated hydrolysis and subsequent release of polyamine domains; and in the subacute phase, the exposed polyamines neutralize cytotoxic aldehydes and sequester iron ions to suppress ferroptosis. In vitro, PPPs demonstrated multimodal cytoprotection by attenuating oxidative stress and inflammation in microglial cells under hemin/cfDNA challenge, thereby preserving neuronal viability, and directly inhibiting neuronal ferroptosis via downregulating heme oxygenase-1 and activating glutathione peroxidase 4/solute carrier family 7 member 11. In vivo, PPPs conferred comprehensive neuroprotection, significantly limiting hematoma expansion, reducing oxidative stress and neuroinflammation, and preventing iron-mediated neuronal death. By precisely interfacing with dynamic pathophysiology of ICH, this tunable nanotherapeutic platform represents a paradigm shift in targeted neurovascular injury management.

脑出血（ICH）是一种危及生命的神经系统疾病，其特征是时空演变的病理级联，需要动态适应其多相损伤进展的干预措施。在这里，我们报告了基于模块化聚合物（PPP）的纳米疗法，通过顺序药理作用设计用于脑出血的阶段特异性治疗。PPP结构将亲水段和疏水段、活性氧（ROS）响应基序集成到多胺支架上，实现ROS触发的程序性解离、按需释放抗炎剂和铁螯合。这种设计赋予了时空治疗精度：在超急性期，PPP纳米颗粒促进快速止血并有效清除无细胞DNA (cfDNA)；在急性期，它们通过ros介导的水解和随后的多胺结构域释放来减轻神经炎症；在亚急性期，暴露的多胺中和细胞毒性醛并隔离铁离子以抑制铁凋亡。在体外，PPPs通过减轻hemin/cfDNA刺激下小胶质细胞的氧化应激和炎症，从而保持神经元活力，并通过下调血红素氧化酶-1和激活谷胱甘肽过氧化物酶4/溶质载体家族7成员11直接抑制神经元铁凋亡，显示出多模式的细胞保护作用。在体内，PPPs具有全面的神经保护作用，显著限制血肿扩张，减少氧化应激和神经炎症，并防止铁介导的神经元死亡。通过与脑出血的动态病理生理学精确结合，这种可调的纳米治疗平台代表了靶向神经血管损伤管理的范式转变。

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引用次数: 0

Harnessing piezoelectric stimulation to modulate PI3K-AKT signaling for intervertebral disc regeneration 利用压电刺激调节PI3K-AKT信号传导促进椎间盘再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-12 DOI: 10.1016/j.bioactmat.2025.12.005

Yisi Liu , Jie Hu , Yu Qian , Qian Wu , Yan Su , Hao Jiang , Hui He , Qianglong Chen , Qifan Yu , Qiang Yang , Ting Liang , Caihong Zhu , Zhangqin Yuan , Houfeng Zheng , Fengxuan Han , Bin Li

Low back pain affects 70–85 % of adults globally, with intervertebral disc degeneration (IVDD) driving nearly half of cases. Integrating human genetic evidence from a large-scale genome-wide association study in up to 829,699 participants along with immunofluorescence staining of nucleus pulposus in patients with varying degrees of IVDD, we identified PI3K-Akt signaling as a central pathway in lumbar disc herniation. Guided by this genetic blueprint, we engineered a piezoelectric scaffold GelMA-FF (GF) which can transform physiological loading into regenerative bioelectrical signals, and regulate PI3K-Akt pathway. The GF system synergizes gelatin methacryloyl's biomechanical compatibility with diphenylalanine crystals' piezoelectric capacity, directly targeting fixed charge density restoration—the electrophysiological hallmark of IVDD. The results reveal that GF-generated electrical signals could change the pathogenic PI3K-Akt/NF-κB axis, shifting disc metabolism from inflammatory catabolism to anabolic regeneration. This GF system also enhances mitochondrial energetics and extracellular matrix synthesis, achieving structural and functional recovery in preclinical models. This study proposes a novel strategy—a paradigm where genetic risk architectures guide physiology-matched biomaterials to transduce endogenous mechanical microenvironment cues into regeneration signals.

全球70 - 85%的成年人患有腰痛，其中近一半的病例由椎间盘退变（IVDD）引起。综合829,699名参与者的大规模全基因组关联研究的人类遗传学证据，以及不同程度IVDD患者髓核的免疫荧光染色，我们确定PI3K-Akt信号通路是腰椎间盘突出症的中心途径。在这一基因蓝图的指导下，我们设计了一种压电支架GelMA-FF (GF)，它可以将生理负荷转化为再生的生物电信号，并调节PI3K-Akt通路。GF系统将明胶甲基丙烯酰的生物力学相容性与二苯丙氨酸晶体的压电能力协同作用，直接针对固定电荷密度恢复- IVDD的电生理标志。结果表明，gf产生的电信号可以改变致病PI3K-Akt/NF-κB轴，使椎间盘代谢从炎症分解代谢转变为合成代谢再生。GF系统还增强线粒体能量和细胞外基质合成，在临床前模型中实现结构和功能恢复。本研究提出了一种新的策略-遗传风险架构引导生理匹配的生物材料将内源性机械微环境线索转化为再生信号的范例。

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引用次数: 0

Adhesive bioactive materials in ocular applications: Toward smart, regenerative, and minimally invasive therapies 黏附生物活性材料在眼部的应用：走向智能、再生和微创治疗

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-12 DOI: 10.1016/j.bioactmat.2025.12.004

Yifei Niu , Saiqun Li , Fei Yu , Xuan Zhao , Jin Yuan

Ocular adhesive bioactive materials represent a paradigm shift in ophthalmic surgery and tissue repair, offering sutureless solutions with enhanced biocompatibility, reduced complications, and improved clinical outcomes. Designed to function as sealants, defect fillers, and delivery vehicles for drugs or cells, these materials must meet the stringent physiological and optical demands of the ocular environment. They are typically classified by anatomical application (ocular surface vs. fundus) and material origin (natural vs. synthetic), and rely on diverse crosslinking strategies to achieve tailored mechanical and adhesive properties. Current design approaches increasingly embrace biomimetic principles—aiming to replicate the structural and functional characteristics of native ocular tissues—to improve integration and therapeutic effectiveness. Moreover, the combination of adhesive materials with regenerative therapies such as stem cells, and exosomes extends their potential from simple structural support to active tissue regeneration. This review provides a comprehensive synthesis of ocular adhesive bioactive materials, outlines major design strategies and applications, and highlights future directions toward personalized and programmable regenerative platforms capable of addressing complex ophthalmic challenges.

眼胶粘剂生物活性材料代表了眼科手术和组织修复的范式转变，提供无缝合线解决方案，增强生物相容性，减少并发症，改善临床结果。这些材料被设计为密封剂、缺陷填充物和药物或细胞的运载工具，必须满足眼部环境严格的生理和光学要求。它们通常根据解剖应用（眼表与眼底）和材料来源（天然与合成）进行分类，并依靠不同的交联策略来实现定制的机械和粘合性能。目前的设计方法越来越多地采用仿生原理，旨在复制天然眼组织的结构和功能特征，以提高整合和治疗效果。此外，粘附材料与再生疗法（如干细胞和外泌体）的结合将其潜力从简单的结构支持扩展到活跃的组织再生。本文综述了眼部黏附生物活性材料的综合合成，概述了主要的设计策略和应用，并强调了能够解决复杂眼科挑战的个性化和可编程再生平台的未来发展方向。

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引用次数: 0

Extracellular vesicles from IPFP-MSCs trigger osteoarthritis by transferring mtDNA IPFP-MSCs的细胞外囊泡通过转移mtDNA引发骨关节炎

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-11 DOI: 10.1016/j.bioactmat.2025.11.046

Shiyu Li , Zi Yan , Xinwang Zhi , Weihan Zheng , Ziqi Zhang , Zhenning Dai , Wanying Chen , Hui Lu , Ziyi Feng , Ting Cheng , Wenhui Liu , Baoyu Sun , Yuhai Ma , Bing Zhang , Jianyuan Zhao , Han Liu , Jiacan Su

Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) extracellular vesicles (EVs) are found to be capable of accelerating Osteoarthritis (OA) progression. However, which pathways and which pathogenic EVs subgroups are involved are not defined. In our study we found that there were a higher percentage of TOMM20⁺ EV's within the total synovial fluid EV's from OA patients than from trauma patients as well as increased mtDNA content. This implicates the mitochondria derived EV sub-group - mitochondria derived vesicles (MDVs) as a potential driver in OA. We found with the single-cell data that MDVs may be secreted from IPFP-MSCs with VPS35. Furthermore, these cells were harvested from the body of the OA patient. IPFP-MSC derived MDVs can deliver exogenous mtDNA to chondrocytes by fusing directly, thus inhibiting chondrocyte matrix synthesis, inducing mitochondrial dysfunction, and activating pro-inflammatory signaling cascades in chondrocytes. Protein microarrays showed that MDVs delivered exogenous mtDNA to chondrocytes, which then activated the cGAS-STING pathway and downstream inflammatory mediators (TBK1, NF-κB, TNF-α). Intra-articular MDV injection worsened cartilage degradation and synovitis in OA rats but STING inhibition alleviated them. This study showed that IPFP-MSC-derived MDVs are essential for OA pathogenesis via mtDNA transfer and cGAS-STING pathway activation. These results show how the mitochondria and immune system talk to each other in the joints causing pain and destroying the cartilage, MDVs are new things that can tell us if someone has this disease and help doctors fix it. Pharmacological blockade of the cGAS-STING axis has shown therapeutic potential, providing a dual approach to mitigate mitochondrial stress and innate immune hyperactivation in OA.

髌下脂肪垫间充质干细胞（IPFP-MSCs）细胞外囊泡（ev）被发现能够加速骨关节炎（OA）的进展。然而，涉及哪些途径和哪些致病性ev亚群尚未确定。在我们的研究中，我们发现OA患者的总滑液EV中TOMM20+ EV的百分比高于创伤患者，并且mtDNA含量增加。这暗示线粒体来源的EV亚群-线粒体来源的囊泡（mdv）是OA的潜在驱动因素。我们通过单细胞数据发现，mpv可能从IPFP-MSCs中分泌。此外，这些细胞来自OA患者的身体。IPFP-MSC衍生的mdv可以通过直接融合将外源mtDNA传递到软骨细胞，从而抑制软骨细胞基质合成，诱导线粒体功能障碍，激活软骨细胞内促炎信号级联反应。蛋白质微阵列显示，mdv将外源性mtDNA传递到软骨细胞，然后激活cGAS-STING途径和下游炎症介质（TBK1, NF-κB, TNF-α）。关节内注射MDV加重OA大鼠软骨退化和滑膜炎，抑制STING可减轻软骨退化和滑膜炎。本研究表明ipfp - msc衍生的mdv通过mtDNA转移和cGAS-STING通路激活对OA发病至关重要。这些结果表明，线粒体和免疫系统如何在关节中相互交流，导致疼痛并破坏软骨，mdv是一种新的东西，可以告诉我们是否有人患有这种疾病，并帮助医生治疗它。药物阻断cGAS-STING轴已显示出治疗潜力，提供了一种双重途径来减轻OA的线粒体应激和先天免疫过度激活。

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引用次数: 0

EDAC-mediated O-acylisourea rearrangement for tertiary amine cationization of hyaluronic acid (HA) and its application as structural backbones in virus-inspired polyplexes edac介导的o -酰基异脲重排对透明质酸（HA）叔胺阳离子化及其在病毒激发多聚体中作为结构主干的应用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-11 DOI: 10.1016/j.bioactmat.2025.12.012

Yinghao Li , Liang Yao , Jiahao Liu , Yi Situ , Chunyu Zhao , Tianyu Mao , Xi Wang , Rijian Song , Hongyun Tai , Zhonglei He , Jing Lyu , Wenxin Wang

Cationic modification of hyaluronic acid (HA) is challenging due to its polyanionic nature, poor reactivity in water, and the instability of conventional coupling intermediates. This limits the development of HA-based components in non-viral gene delivery systems, which already suffer from amorphous morphology and mechanical fragility that reduce their transfection efficiency. Here, we reprogram a classically unfavorable EDAC-mediated rearrangement into a productive synthetic route, enabling direct cationization of hyaluronic acid (HA) through spontaneous O-acylisourea rearrangement. This water-based, catalyst-free process achieves up to 70 % substitution of HA's carboxyl groups—introducing cationic tertiary amine functionalities in water. The resulting aminated-hyaluronic acid (HAA) scaffolds act as rigid structural backbones in virus-inspired polymer–DNA nanoparticles termed as “Skeletoplexes”, with enhanced stability and performance. When incorporated into polyplexes formed from diverse cationic systems—including poly(β-amino esters) and commercial vectors such as BrPERfect, Xfect, jetPEI, and Lipofectamine3000—HAA scaffolds improved in vitro transfection efficiency by up to 4-fold and in vivo gene expression by approximately 2-fold. These results establish a generalizable and green scaffold-based strategy that bridges the structural and functional gap between viral and non-viral gene delivery vectors.

透明质酸（HA）的阳离子改性具有挑战性，因为它的多阴离子性质，在水中的反应性差，以及传统偶联中间体的不稳定性。这限制了在非病毒基因传递系统中基于ha的组件的发展，这些组件已经受到无定形形态和机械脆弱性的影响，降低了它们的转染效率。在这里，我们将传统上不利的edac介导的重排重新编程为高效的合成路线，通过自发的o -酰基异脲重排实现透明质酸（HA）的直接阳离子化。这种基于水的，无催化剂的工艺实现了高达70%的HA的羧基取代-在水中引入阳离子叔胺功能。由此产生的氨基透明质酸（HAA）支架在病毒激发的聚合物- dna纳米颗粒（称为“骨架”）中充当刚性结构骨架，具有增强的稳定性和性能。当纳入由不同阳离子体系（包括聚β-氨基酯）和商业载体（如BrPERfect， xeffect， jetPEI和lipofectamine3000）形成的多聚物时，haa支架的体外转染效率提高了4倍，体内基因表达提高了约2倍。这些结果建立了一个可推广的绿色支架策略，在病毒和非病毒基因传递载体之间的结构和功能上架起了桥梁。

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引用次数: 0

Apoptotic metabolites synthesize and inherit unique de novo L2a/L2b RNAs to prevent virus infection 凋亡代谢物合成和遗传独特的新生L2a/L2b rna以防止病毒感染

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-10 DOI: 10.1016/j.bioactmat.2025.11.035

Peiyi Li , Yelin Lan , Xutong Yan , Zeyuan Cao , Jingyun Ji , Mingqiang Deng , Dongmei He , Ruoxin Huang , Yan Qu , Yaoxing Wu , Xinchun Zhang , Jun Cui , Guanzheng Luo , Xichen Bao , Songtao Shi

Apoptosis is indispensable for a variety of physio-pathological processes. RNA is one of essential macromolecules for life. Extensive RNA decay is a characteristic feature of apoptosis. However, it is unknown whether there is de novo RNA synthesis in apoptotic cells and metabolites. In this study, we show that apoptotic mesenchymal stem cells (MSCs) and their apoptotic vesicles (apoVs) synthesize de novo RNAs. Nascent RNA-seq showed apoptotic MSCs and apoVs produced numerous nascent RNAs that were different from those in living MSCs, including protein-coding and non-coding RNAs. Mechanistically, apoptotic de novo RNA synthesis was related to the caspase-3/Sp1/RNA polymerase axis. Additionally, we found the LINE-2a (L2a) and LINE-2b (L2b) RNAs were specifically transcribed in apoptotic MSCs and transferred into apoVs to prevent virus infection. Altogether, this study reveals a previously unknown phenomenon that apoptotic cells synthesize various de novo RNAs and identifies that apoptotic LINE-2 RNAs can regulate innate immunity to prevent virus infection.

细胞凋亡在多种生理病理过程中不可或缺。RNA是生命所必需的大分子之一。广泛的RNA衰变是细胞凋亡的一个特征。然而，凋亡细胞及其代谢产物中是否存在从头RNA合成尚不清楚。在这项研究中，我们发现凋亡的间充质干细胞（MSCs）和它们的凋亡囊泡（apoVs）可以合成新的rna。新生RNA-seq显示凋亡的MSCs和apoVs产生了许多不同于活的MSCs的新生rna，包括蛋白质编码rna和非编码rna。机制上，凋亡新生RNA合成与caspase-3/Sp1/RNA聚合酶轴有关。此外，我们发现LINE-2a （L2a）和LINE-2b (L2b) rna在凋亡的MSCs中特异性转录并转移到apov中以防止病毒感染。总之，本研究揭示了一个以前未知的现象，即凋亡细胞合成各种新生rna，并确定凋亡的LINE-2 rna可以调节先天免疫以预防病毒感染。

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引用次数: 0

Chiral metal nanozyme-enabled SOD2 activation and siRNA delivery cooperatively mitigating chronic heart failure 手性金属纳米酶激活SOD2和siRNA递送协同缓解慢性心力衰竭

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-09 DOI: 10.1016/j.bioactmat.2025.11.049

Zekun Wang , Ruofei Zhang , Yanyu Hu , Qile Song , Xiaoyan Fu , Yifan Wang , Mei Chen , Kelong Fan , Cundong Fan , Dongdong Sun

Doxorubicin (DOX) treatment can lead to intracellular iron overload in cardiomyocytes, triggering excessive generation of reactive oxygen species (ROS) and resulting in cardiotoxicity. Superoxide dismutase (SOD) effectively scavenges ROS, and its catalytic activity depends on the binding of metal ions at its active site. Therefore, enhancing the activity of metal-dependent SOD represents a promising strategy to inhibit ferroptosis in cardiomyocytes and alleviate DOX-induced chronic heart failure. In this study, we constructed a biomimetic chiral MnO₂ nanozyme co-modified with macrophage and platelet membranes (D/L-MnO₂@MM), enabling precise targeting of DOX-injured myocardial tissues. This nanozyme exhibited potent catalase-like and SOD-like activities, efficiently eliminating excessive local hydrogen peroxide (H₂O₂) and superoxide anions (O₂^•−). Notably, the D-enantiomeric nanozyme (D-MnO₂@MM) significantly enhanced endogenous SOD2 activity via Mn²⁺ ion release, thereby suppressing the accumulation of lipid peroxides. Furthermore, based on transcriptomic and proteomic analyses, we designed an siRNA targeting the Hmox1 gene (siHmox1) and successfully loaded it onto the nanozyme platform (siHmox1@D/L-MnO₂@MM). Both in vitro and in vivo experiments confirmed that the dual mechanism, SOD2 activation and Hmox1 silencing, effectively restored mitochondrial function, attenuated ferroptosis, and significantly improved cardiac function in a rat model of chronic heart failure. Collectively, this study proposes a novel ferroptosis-targeted therapeutic strategy based on a biomimetic chiral nanozyme, offering new insights and promising therapeutic potential for the treatment of DOX-induced cardiotoxicity.

多柔比星（DOX）治疗可导致心肌细胞内铁超载，引发活性氧（ROS）的过量产生，并导致心脏毒性。超氧化物歧化酶（SOD）能有效清除活性氧，其催化活性取决于其活性位点上金属离子的结合。因此，增强金属依赖性SOD的活性是抑制心肌细胞铁下沉和减轻dox诱导的慢性心力衰竭的一种有希望的策略。在这项研究中，我们构建了一种与巨噬细胞和血小板膜共修饰的仿生手性MnO2纳米酶（D/L-MnO2@MM），可以精确靶向dox损伤的心肌组织。该纳米酶表现出类似过氧化氢酶和类似sod的活性，能有效去除过量的过氧化氢（H2O2）和超氧阴离子（O2•−）。值得注意的是，d -对映体纳米酶（D-MnO2@MM）通过Mn2+离子释放显著增强内源性SOD2活性，从而抑制脂质过氧化物的积累。此外，基于转录组学和蛋白质组学分析，我们设计了一个靶向Hmox1基因的siRNA (siHmox1)，并成功地将其加载到纳米酶平台（siHmox1@D/L-MnO2@MM）上。体外和体内实验均证实了SOD2激活和Hmox1沉默的双重机制，在慢性心力衰竭大鼠模型中有效恢复线粒体功能，减轻铁下沉，显著改善心功能。总之，本研究提出了一种基于仿生手性纳米酶的新的针对铁中毒的治疗策略，为治疗dox诱导的心脏毒性提供了新的见解和有希望的治疗潜力。

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引用次数: 0

Fishnet-like 2D magnetic nanozyme probe enables ultrasensitive bedside immunodiagnosis of bone infection pathogens 鱼网状二维磁性纳米酶探针使骨感染病原体的超灵敏床边免疫诊断成为可能

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-09 DOI: 10.1016/j.bioactmat.2025.11.043

Chongwen Wang , Changyue Xu , Jiaxuan Li , Ting Wu , Kaijie Guo , Bingjie Wang , Junyan Ai , Limin Ma , Bing Gu , Yuanchen Ma

Rapid, early, and accurate bedside diagnosis of bone infections is an urgent clinical need that remains unmet. Here, we present a fishnet-like two-dimensional magnetic nanozyme (FGDAI) that integrates three functional modules: a monolayer graphene oxide substrate providing a large reaction interface; an Fe₃O₄ interlayer conferring efficient magnetic enrichment; and two dense layers of Au@Ir nanoparticles furnishing abundant catalytic sites that act synergistically with the Fe₃O₄ to enable catalytic enhancement. This architecture delivers multiple signal amplification—“large reaction interface, magnetic enrichment, synergistic enhancement”—within an immunochromatographic assay (ICA), effectively overcoming the sensitivity and robustness limitations of traditional colorimetric ICAs when challenged by complex clinical matrices. In addition, wheat germ agglutinin (WGA) was immobilized on the 2D FGDAI surface via lyophilization as a universal peptidoglycan recognition molecule, enabling efficient, broad-spectrum bacterial binding and thereby mediating ultrasensitive, simultaneous ICA detection of two important bone-infection pathogens (Staphylococcus aureus and Pseudomonas aeruginosa). FGDAI-WGA-ICA completes testing in under 25 min with a visual limit of detection of 10 cells/mL, exhibiting high sensitivity and specificity for the target pathogens. Moreover, validation in a cohort of 83 synovial fluid samples showed high concordance with clinical reference methods, supporting its potential for real-time, bedside diagnosis of bone infections.

快速，早期，准确的床边诊断骨感染是一个迫切的临床需要，仍然没有得到满足。在这里，我们提出了一种鱼网状的二维磁性纳米酶（FGDAI），它集成了三个功能模块：单层氧化石墨烯衬底提供了一个大的反应界面；Fe3O4中间层具有高效的磁富集作用；两层致密的Au@Ir纳米颗粒提供丰富的催化位点，与Fe3O4协同作用，实现催化增强。这种结构在免疫层析分析（ICA）中提供多重信号放大-“大反应界面，磁富集，协同增强”，有效克服了传统比色法ICA在复杂临床基质挑战时的灵敏度和鲁棒性限制。此外，通过冻干将小麦胚芽凝集素（WGA）作为一种通用肽聚糖识别分子固定在二维FGDAI表面，实现了高效、广谱的细菌结合，从而介导了两种重要的骨感染病原体（金黄色葡萄球菌和铜绿假单胞菌）的超灵敏、同时的ICA检测。FGDAI-WGA-ICA在25分钟内完成检测，视觉检测限为10个细胞/mL，对目标病原体具有很高的灵敏度和特异性。此外，83个滑液样本的队列验证显示与临床参考方法高度一致，支持其用于骨感染的实时床边诊断的潜力。

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引用次数: 0

Corrigendum to “Skin-inspired phototherapeutic cryogel ameliorates infected wound healing by orchestrating mechanotransduction and immunomodulation” [Bioact. Mater. 57 (2026) 768–790] “皮肤启发的光疗低温凝胶通过协调机械传导和免疫调节改善感染伤口愈合”的更正[Bioact]。[57 (2026) 768-790]

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-12-08 DOI: 10.1016/j.bioactmat.2025.12.003

Sayan Deb Dutta , Jeong Man An , Md Moniruzzaman , Rumi Acharya , Youjin Seol , Hojin Kim , Aayushi Randhawa , Jong-Sung Kim , Yong-kyu Lee , Ki-Taek Lim

引用次数: 0