Materials Today Bio最新文献_第6页

A purpurin-based metalloimmunostimulant amplifies ROS and modulates STING/TNF-α axis to potentiate melanoma immunotherapy 一种基于紫癜蛋白的金属免疫刺激剂可以放大ROS并调节STING/TNF-α轴，从而增强黑色素瘤的免疫治疗。

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-21 DOI: 10.1016/j.mtbio.2026.102804

Xiaoxin Yang , Mi Huang , Tianyi Pang , Dong Zhong , Hong Liu , Xiang Chen , Jun Liu , Yu Wen

The low infiltration of pro-inflammatory immune cells and the sustained activation of multiple immunosuppressive signaling pathways in melanoma significantly limit the efficacy of clinical immunotherapy. Therefore, developing an effective immunostimulant with reversing the immunosuppressive tumor microenvironment (TME) is of great significance for improving melanoma immunotherapy. Herein, a degradable metalloimmunostimulant (PurpN/Mn@PEG) is developed for immunotherapy targeting immunosuppressive melanoma. The PurpN/Mn@PEG NPs are fabricated by coordination-driven self-assembly of purpurin and Mn²⁺, followed by polyethylene glycol (PEG) modification. PurpN/Mn@PEG dissociates in acidic pH and high glutathione TME, releasing PurpN and Mn²⁺. The nanoparticle exhibits peroxidase-/oxidase-like activity, generating a reactive oxygen species (ROS) storm that induces immunogenic cell death. PurpN/Mn@PEG amplifies ROS via H₂O₂ production through phenolic oxidation, enhances TNF-α secretion via CCAAT/enhancer-binding protein beta (CEBPB) upregulation, and sensitizes cGAS-STING pathway, synergistically boosting melanoma immunotherapy. In vivo experiments demonstrated that this purpurin-based metalloimmunostimulant exhibits remarkable therapeutic efficacy with an 87.8 % tumor growth inhibition rate in B16-F10 melanoma-bearing mice by activating multiple immune pathways, thereby effectively augmenting melanoma immunotherapy. This study provides an innovative therapeutic strategy that effectively reprograms the immunosuppressive TME to potentiate melanoma immunotherapy.

黑色素瘤中促炎免疫细胞的低浸润和多种免疫抑制信号通路的持续激活显著限制了临床免疫治疗的疗效。因此，开发一种能够逆转免疫抑制肿瘤微环境（immunosuppressive tumor microenvironment， TME）的有效免疫刺激剂，对于改善黑色素瘤免疫治疗具有重要意义。本文开发了一种可降解的金属免疫刺激剂（PurpN/Mn@PEG），用于针对免疫抑制性黑色素瘤的免疫治疗。PurpN/Mn@PEG NPs是通过配位驱动的purpurin和Mn2+自组装，然后进行聚乙二醇（PEG）修饰制备的。PurpN/Mn@PEG在酸性pH和高谷胱甘肽TME下解离，释放PurpN和Mn2+。纳米颗粒表现出过氧化物酶/氧化酶样活性，产生活性氧（ROS）风暴，诱导免疫原性细胞死亡。PurpN/Mn@PEG通过酚类氧化产生H2O2来扩增ROS，通过CCAAT/增强子结合蛋白β (CEBPB)上调来增强TNF-α分泌，并使cGAS-STING通路增敏，协同促进黑色素瘤免疫治疗。体内实验表明，这种基于紫癜蛋白的金属免疫刺激剂通过激活多种免疫途径，对B16-F10黑色素瘤小鼠的肿瘤生长抑制率达到87.8%，有效增强了黑色素瘤的免疫治疗效果。这项研究提供了一种创新的治疗策略，有效地重新编程免疫抑制TME，以增强黑色素瘤的免疫治疗。

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引用次数: 0

Engineered targeted Ce-based MOF nanozymes for ROS scavenging and inflammatory Reprogramming in chronic pancreatitis 基于ce的MOF纳米酶用于慢性胰腺炎的ROS清除和炎症重编程

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-21 DOI: 10.1016/j.mtbio.2026.102811

Yongkang Lai , Yongliang Ouyang , Xiaojing Yin , Tao Yu , Jianhua Wan , Xueyang Li , Yi Hu , Xu Shu , Huan Wang

Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal–organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered in vivo, the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce³⁺ and Ce⁴⁺, while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.

慢性胰腺炎（CP）是一种终身进行性纤维化炎症性疾病，目前尚无有效的治疗方法。活性氧（ROS）诱导的持续和复发性炎症刺激是胰腺纤维形成的关键驱动因素，使氧化应激成为阻止疾病进展的有希望的治疗靶点。在这项研究中，我们开发了一种纳米系统HC@CeMOF，由一个小尺寸的铈基金属有机框架（CeMOF）核心组成，该核心装载姜黄素并涂覆透明质酸（HA），能够精确靶向炎症胰腺组织。HC@CeMOF表现出小尺寸的颗粒尺寸以及良好的细胞和生物安全性。一旦在体内给药，纳米系统利用HA与巨噬细胞上CD44受体的特异性结合亲和力，选择性地积聚在炎症胰腺部位。随后，铈基纳米酶通过Ce3+和Ce4+之间的可逆氧化还原循环有效清除ROS，而姜黄素的缓慢释放进一步抑制NF-κB信号通路，调节炎症细胞因子水平，从而达到协同抗炎和抗氧化的作用。总的来说，这些机制实质上减弱了CP的进展。这种靶向ros清除和抗炎策略有望成为慢性胰腺炎的替代治疗方法。

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引用次数: 0

Advancing precision tumor therapy: Progress in targeted delivery of peptide-based nanomaterials from microenvironment to organelles 推进精准肿瘤治疗：肽基纳米材料从微环境靶向递送到细胞器的研究进展

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-21 DOI: 10.1016/j.mtbio.2026.102820

Kexin Tian , Jiabao Sheng , Jiao Chen , Mingjun Zhang , Jiarui Song , Manqing Wu , Yinan Zhao , Shubiao Zhang

Precisely targeted delivery of antitumor agents is a key strategy for enhancing cancer treatment efficacy. By leveraging specific tumor characteristics, functional modifications can construct highly selective delivery systems to optimize nanomedicine distribution at tumor sites. Owing to their editable sequences, peptides can be engineered into various targeting ligands for nanomaterial functionalization. Through specific receptor-ligand interactions, these modified nanomaterials achieve enhanced tumor-specific localization and deep penetration, enabling precise therapeutic agent delivery and improved treatment outcomes. This paper systematically reviews recent advances in peptide-based nanomaterials for tumor-targeted therapy. Based on molecular recognition, we present their applications in targeting the tumor microenvironment (TME) (including vasculature,immune cells, extracellular matrix, and associated fibroblasts), tumor cells, and organelles (such as mitochondria, endoplasmic reticulum [ER], Golgi apparatus, and nucleus). Furthermore, we provide an in-depth discussion of the opportunities and challenges these materials face in drug-targeted delivery, aiming to support the advancement of tumor-targeting nanomedicine.

精确靶向给药是提高肿瘤治疗效果的关键策略。通过利用特定的肿瘤特征，功能修饰可以构建高选择性的给药系统，以优化纳米药物在肿瘤部位的分布。由于其可编辑的序列，肽可以被设计成各种靶向配体，用于纳米材料的功能化。通过特异性受体-配体的相互作用，这些修饰的纳米材料实现了增强的肿瘤特异性定位和深度渗透，从而实现了精确的治疗剂递送和改善的治疗效果。本文系统地综述了肽类纳米材料在肿瘤靶向治疗中的研究进展。基于分子识别，我们介绍了它们在靶向肿瘤微环境（TME）（包括脉管系统、免疫细胞、细胞外基质和相关成纤维细胞）、肿瘤细胞和细胞器（如线粒体、内质网、高尔基体和细胞核）方面的应用。此外，我们还深入讨论了这些材料在药物靶向递送中面临的机遇和挑战，旨在支持肿瘤靶向纳米医学的发展。

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引用次数: 0

A multiscale quantum dots-based material platform for high-performance immunosensing of rhinitis biomarkers 基于多尺度量子点的鼻炎生物标志物高效免疫传感材料平台

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-21 DOI: 10.1016/j.mtbio.2026.102839

Jingqiu Chen , Hegeng Li , Yanbing Tao , Wenjian Zhang , Xinyi Chen , Yunong Zhao , Lanpeng Guo , Qing Huang , Jianjun Chen , Huan Liu

Rhinitis is a common chronic respiratory disease that severely affects patients' quality of life and may lead to serious complications, underscoring the need for rapid and portable diagnostic tools to support routine monitoring and clinical management. Here, we introduce a multiscale material platform based on colloidal quantum dots (CQDs) for the construction of electrochemical immunosensors enabling the rapid detection of eosinophil cationic protein (ECP) and neutrophil myeloperoxidase (MPO), two clinically relevant biomarkers of rhinitis. The platform leverages specific antigen–antibody recognition coupled with the electrical transduction properties of CQDs, resulting in significant improvement of detection sensitivity. To ensure translational applicability, we systematically examined key factors associated with real clinical samples, including hemolysis, storage duration, and preservation conditions in serum, and verified the method's reliability through spiked recovery experiments. More over, the immunosensor was successfully applied to the detection of ECP and MPO in patient-derived nasal secretion samples, exhibiting strong concordance with enzyme-linked immunosorbent assay (ELISA) results. Collectively, this work demonstrates that the CQD-based material platform offers a robust and clinically validated strategy for protein biomarker detection, and highlights its strong potential for home-based diagnostics, providing valuable support for the early diagnosis and management of rhinitis.

鼻炎是一种常见的慢性呼吸道疾病，严重影响患者的生活质量，并可能导致严重的并发症，强调需要快速和便携式诊断工具来支持常规监测和临床管理。在这里，我们介绍了一个基于胶体量子点（CQDs）的多尺度材料平台，用于构建电化学免疫传感器，能够快速检测嗜酸性粒细胞阳离子蛋白（ECP）和中性粒细胞髓过氧化物酶（MPO），这两个临床相关的鼻炎生物标志物。该平台利用特异性抗原抗体识别和CQDs的电转导特性，显著提高了检测灵敏度。为了确保翻译的适用性，我们系统地检查了与真实临床样品相关的关键因素，包括溶血、保存时间和血清保存条件，并通过加标回收率实验验证了该方法的可靠性。此外，该免疫传感器成功应用于患者源性鼻分泌物样本中ECP和MPO的检测，与酶联免疫吸附试验（ELISA）结果具有很强的一致性。总之，这项工作表明，基于cqd的材料平台为蛋白质生物标志物检测提供了一种强大的、经临床验证的策略，并突出了其在家庭诊断方面的强大潜力，为鼻炎的早期诊断和管理提供了有价值的支持。

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引用次数: 0

Intravesical folate-conjugated hydroxyethyl starch micelles for pH-triggered co-delivery of epirubicin and TLR7 agonist toward synergistic chemoimmunotherapy of bladder cancer 膀胱内叶酸偶联羟乙基淀粉胶束用于ph触发的表柔比星和TLR7激动剂的协同化学免疫治疗膀胱癌

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-21 DOI: 10.1016/j.mtbio.2026.102835

Yuxiu Wang , Haoyang Yuan , Ye Zhang , Yu Zhang , Tian Yin , Haibing He , Xing Tang , Yanjiao Wang , Jingxin Gou , Guofei Li

The immunosuppressive tumor microenvironment and poor drug targeting remain major obstacles in bladder cancer (BC) therapy. To address this, a combination strategy integrating chemotherapy and immunotherapy was employed by co-delivering epirubicin (EPI) and the immune modulator imiquimod (IMQ) using a folate-modified nanocarrier. A hydroxyethyl starch-based epirubicin prodrug modified with folic acid (FA-HES-EPI) was first synthesized to improve tumor selectivity. FA-HES-EPI/IMQ micelles were then fabricated via nanoprecipitation by encapsulating IMQ into the hydrophobic core, aiming to achieve synergistic therapeutic efficacy. Folate modification conferred tumor-targeting capability to the micelles and promoted efficient cellular uptake via folate receptor–mediated endocytosis. The acid-sensitive hydrazone bond enabled controlled release of both EPI and IMQ in the acidic tumor microenvironment, thereby enhancing their combined chemo-immunotherapeutic effects. In an orthotopic BC model, FA-HES-EPI/IMQ micelles significantly enhanced drug accumulation at the tumor site, repolarized M2-type tumor-associated macrophages (TAMs) toward the M1 phenotype, remodeled the tumor stroma, and achieved a tumor inhibition rate of 96.7 %, markedly surpassing that of FA-HES-EPI micelles (86.6 %) and free EPI (62.3 %), with negligible systemic toxicity. This pH-responsive co-delivery system represents a promising approach to improve both efficacy and safety in bladder cancer treatment.

免疫抑制肿瘤微环境和药物靶向性差仍然是膀胱癌（BC）治疗的主要障碍。为了解决这个问题，采用化疗和免疫治疗的联合策略，使用叶酸修饰的纳米载体共同递送表柔比星（EPI）和免疫调节剂咪喹莫特（IMQ）。首次合成了叶酸修饰羟乙基淀粉基表阿霉素前药（FA-HES-EPI），以提高肿瘤选择性。然后通过纳米沉淀法将IMQ包埋在疏水核中，制备FA-HES-EPI/IMQ胶束，以达到协同治疗的效果。叶酸修饰赋予了胶束肿瘤靶向能力，并通过叶酸受体介导的内吞作用促进了有效的细胞摄取。酸敏感的腙键使EPI和IMQ在酸性肿瘤微环境中可控释放，从而增强了它们的化学免疫联合治疗效果。在原位BC模型中，FA-HES-EPI/IMQ胶束显著增强了肿瘤部位的药物积累，使m2型肿瘤相关巨噬细胞（tam）向M1表型重新极化，重塑了肿瘤基质，并实现了96.7%的肿瘤抑制率，明显超过FA-HES-EPI胶束（86.6%）和游离EPI(62.3%)，而全身毒性可忽略不计。这种ph反应性的共给药系统代表了一种有希望的方法来提高膀胱癌治疗的有效性和安全性。

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引用次数: 0

Synergistic 3D-bioprinted scaffold with multi-level adaptability for vascularized bone regeneration via osteogenesis-angiogenesis coupling 通过成骨-血管生成耦合实现血管化骨再生的协同3d生物打印支架

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-21 DOI: 10.1016/j.mtbio.2026.102837

Ji Yin , Xiaojun Mao , Panpan Shang , Shuo Chen , Guang Yang , Hongtao He , Chuanglong He , Xiaojun Zhou

3D bioprinting enables the fabrication of biomimetic, cell-laden and pro-osteogenic constructs with high precision for bone regeneration. The ability of integrating favorable mechanical strength and multi-material interactive bioactivity in engineered constructs for efficient bone defect repair is still a challenge. Herein, we employed a dual-nozzle synergistic 3D bioprinting technology to fabricate a biocomposite scaffold that integrated interactive soft hydrogel filaments and hard polycaprolactone (PCL)-based filaments by mimicking weave patterns. The multi-material scaffold design aimed at providing features of suitable microstructure and long-term mechanical support, enhanced vascularized bone regeneration for bone repair. Chitosan/hyaluronic acid functionalized mesoporous silica nanoparticles bearing osteogenic protein on the surface and angiogenic drug in the pores were embedded into cell-supportive hydrogel bioink for promoting osteogenesis-angiogenesis coupling. Meanwhile, MgO nanoparticles were incorporated into structure-supportive PCL matrix for improving mechanical strength and compensating angiogenic/osteogenic activities by sustained release of Mg²⁺. The biocomposite scaffold had good cytocompatibility, and could stimulate in vitro angiogenic behavior and osteogenic differentiation. In vivo experiments revealed that the biocomposite scaffolds significantly enhanced vascularization and promoted bone regeneration on the cranial defect model. Overall, this study has offered a promising strategy for fabricating a multi-level adaptable 3D-bioprinted scaffold for bone defect repair through osteogenesis-angiogenesis coupling.

3D生物打印能够制造具有高精度的骨再生仿生，细胞负载和促骨结构。将良好的机械强度和多材料相互作用的生物活性整合到工程结构中以实现有效的骨缺损修复的能力仍然是一个挑战。在此，我们采用双喷嘴协同3D生物打印技术，通过模拟编织模式，制造了一种生物复合材料支架，该支架集成了相互作用的软水凝胶细丝和硬聚己内酯（PCL）为基础的细丝。多材料支架设计旨在提供合适的微观结构和长期的机械支持，增强血管化骨再生，实现骨修复。将壳聚糖/透明质酸功能化的介孔二氧化硅纳米颗粒包埋在支持细胞的水凝胶生物链中，表面携带成骨蛋白，孔内携带血管生成药物，促进成骨-血管生成耦合。同时，将MgO纳米颗粒加入到结构支持型PCL基质中，通过Mg2+的持续释放来提高机械强度和补偿血管生成/成骨活性。该生物复合支架具有良好的细胞相容性，可刺激体外血管生成行为和成骨分化。体内实验表明，生物复合材料支架可显著增强颅骨缺损模型的血管化，促进骨再生。总的来说，本研究为通过成骨-血管生成耦合修复骨缺损提供了一种有前景的多层适应性3d生物打印支架。

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引用次数: 0

3D bioprinted composite scaffold incorporating microfluidics-derived chondrocyte microspheroids promotes auricular cartilage regeneration 结合微流体衍生软骨细胞微球体的生物3D打印复合支架促进耳廓软骨再生

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-20 DOI: 10.1016/j.mtbio.2026.102826

Xiaolei Chen , Haolei Hu , Jie Yang , Yiwen Wang , Wei Yue , Peimei Xing , Yage Zhang , Jianwei Chen , Tao Xu , Yi Li

Microtia remains a major clinical challenge, as autologous costal cartilage transplantation—the current gold standard—suffers from donor-site morbidity and imprecise morphology, whereas synthetic implants are prone to immune rejection and structural collapse. Here, we present a biphasic composite strategy integrating microfluidics and 3D bioprinting. Organoid-like auricular spheroids generated via microfluidics exhibited a biomimetic architecture, featuring cartilage-specific collagen cores surrounded by organized chondrocytes, with sustained ECM secretion and phenotype maintenance. These bioactive spheroids were subsequently incorporated into a biomimetic bioink and patterned through extrusion-based 3D bioprinting, enabling precise anatomical shaping and functional scaffold construction. Upon implantation in immunodeficient mice, the biphasic constructs promoted rapid in situ cartilage regeneration and ECM deposition, yielding tissue with morphological and histological features closely resembling native auricular cartilage. Collectively, this study demonstrates that the integration of microfluidic spheroids with 3D bioprinting offers a balanced solution between structural fidelity and biological functionality, providing a promising pathway for auricular cartilage reconstruction.

由于自体肋软骨移植（目前的金标准）存在供体部位发病率和形态不精确的问题，而合成植入物容易产生免疫排斥和结构崩溃，因此小缺损仍然是一个主要的临床挑战。在这里，我们提出了一种集成微流体和3D生物打印的双相复合策略。通过微流体生成的类器官样耳廓球体具有仿生结构，其特征是软骨特异性胶原核心被有组织的软骨细胞包围，具有持续的ECM分泌和表型维持。这些生物活性球体随后被整合到仿生生物墨水中，并通过基于挤压的3D生物打印进行图案化，从而实现精确的解剖形状和功能性支架结构。在免疫缺陷小鼠体内植入后，双相构建体促进了快速的原位软骨再生和ECM沉积，产生的组织形态和组织学特征与天然耳廓软骨非常相似。总之，本研究表明，微流控球体与3D生物打印的结合在结构保真度和生物功能之间提供了一个平衡的解决方案，为耳廓软骨重建提供了一个有希望的途径。

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引用次数: 0

Inflammation-targeted single-atom nanozymes drive microglial depolarization and inhibit ferroptosis via Sirt-6-xCT-GPX4 axis to attenuate early brain injury following subarachnoid hemorrhage 炎症靶向单原子纳米酶驱动小胶质细胞去极化并通过Sirt-6-xCT-GPX4轴抑制铁凋亡以减轻蛛网膜下腔出血后早期脑损伤

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-20 DOI: 10.1016/j.mtbio.2026.102829

Boliang Liu , Chao Xiang , Xiaodan Zhang , Wei Guo , Haitao Wu , Fandi Hou , Yueyang Ba , Xiulei Zhang , Zhongcan Chen , Guang Feng , Yuan Dang , Yang Zhu , Jianjun Gu

Early brain injury (EBI) has been identified as a key factor leading to the poor prognosis of patients with subarachnoid hemorrhage (SAH). At present, apart from surgical treatment, there is a lack of effective neuroprotective drugs. In this study, a biomimetic nanozyme V-MDL-800 was constructed by coordinating Vanadium Single-atom enzymes (V/SAE) and the allosteric activator MDL-800 of Sirt6, and encapsulated into NM@V-MDL-800 with neutropenia cell membrane (NM). By clearing ROS, the xCT/GPX4 pathway was activated, blocking the pathophysiological process of EBI after SAH can improve prognosis. NM@V-MDL-800 recruits through the blood-brain barrier (BBB) at the site of hemorrhagic injury by relying on the chemotactic property of neutrophils. Among them, the catalase-like, superoxide dismutase-like, and hydroxyl radical scavenging effects of V/SAE can eliminate excessive reactive oxygen species (ROS) within cells and inhibit oxidative stress; at the same time, as an allosteric activator of Sirt6, it activates the downstream xCT/GPX4 pathway, improving lipid metabolism abnormalities. Regulating the key core pathway of lipid peroxidation on ferroptosis promotes the polarization of microglia from the pro-inflammatory M1 form to the anti-inflammatory M2 morphology to inhibit the pathophysiological process of neuroinflammation in EBI. In addition, in vivo imaging of mice confirmed the targeted effect of NM@V-MDL-800 through the blood-brain barrier and recruited at the site of bleeding injury. The therapeutic effect of NM@V-MDL-800 on the SAH model has also been confirmed in vivo and in vitro experiments. This provides new ideas for SAH drug therapy regimens of SAH targeting microglial ferroptosis.

早期脑损伤（EBI）是导致蛛网膜下腔出血（SAH）患者预后不良的关键因素。目前，除手术治疗外，缺乏有效的神经保护药物。本研究将钒单原子酶（V/SAE）与Sirt6的变构激活剂MDL-800配合构建仿生纳米酶V-MDL-800，并用中性粒细胞减少症细胞膜（NM）包裹在NM@V-MDL-800中。通过清除ROS，激活xCT/GPX4通路，阻断SAH后EBI的病理生理过程，改善预后。NM@V-MDL-800通过出血性损伤部位的血脑屏障（BBB）招募，依靠中性粒细胞的趋化特性。其中，V/SAE具有过氧化氢酶样、超氧化物歧化酶样和羟基自由基清除作用，可消除细胞内过多的活性氧（ROS），抑制氧化应激；同时，作为Sirt6的变构激活剂，激活下游的xCT/GPX4通路，改善脂质代谢异常。调节铁上塌的脂质过氧化关键核心通路，促进小胶质细胞由促炎M1形态向抗炎M2形态极化，抑制EBI神经炎症的病理生理过程。此外，小鼠体内成像证实了NM@V-MDL-800通过血脑屏障在出血性损伤部位招募的靶向作用。NM@V-MDL-800对SAH模型的治疗作用也在体内和体外实验中得到证实。这为SAH靶向小胶质细胞铁下垂的药物治疗方案提供了新的思路。

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引用次数: 0

Colloid-patterned surfaces distinguish malignant mechanophenotypes 胶体图案表面区分恶性机械表型

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102800

Chalom Zemmour , Mor Ozeri , Ora T. Cohen , Eduard Berenshtein , Zakhariya Manevitch , Yael Feinstein-Rotkopf , Irit Rosenhek-Goldian , Hadar Benyamini , Victor Shelukhin , Ofra Benny

Accurate and rapid identification of aggressive cancer cells remains a major clinical challenge. Here, we present a simple, label-free mechanophenotyping platform that integrates controlled colloidal topographies with particle-uptake measurements to reveal biophysical traits associated with metastatic progression. Non-close-packed polystyrene bead arrays were formed on cell culture plates by controlled deposition and stabilized with a thin silicon oxide coating. These arrays display micro- and nano-features with a size range of 0.23–2.3 μm at diverse densities and were used to assess adhesion across cancer cells exhibiting different levels of malignancy. Particle uptake differences were most pronounced for particle diameters above 0.5 μm, whereas adhesion differences emerged predominantly on particles ≥0.7 μm and increased progressively with larger particle sizes. Colloidal topographies were fabricated at particle deposition concentrations of 500 μg/mL and 1000 μg/mL, and adhesion differences were observed under both conditions, with more potent effects at the higher concentration. At the metastatic site, cells exhibited increased particle uptake, stronger adhesion, and a larger morphological engagement on colloid-coated substrates, characterized by extensive actin-rich protrusions wrapping individual particles. AFM force mapping confirmed higher adhesion forces to a colloidal probe, while transcriptomic profiling revealed enrichment of adhesion and ECM-remodeling pathways in the adhesive metastatic state. We also find that lymphatically selected cells exhibit reduced adhesion on colloid-coated surfaces but higher particle uptake compared to the primary tumor cells. These results indicate that after leaving the primary tumor, metastatic cells have reduced adhesive potential, which is only regained upon reaching secondary sites. By exposing adhesion differences that are undetectable on flat substrates and linking them to particle uptake assays, this platform produces functional signatures of metastatic potential. This method is technically accessible, compatible with imaging and molecular workflows, and adaptable for high-throughput or clinical analysis, offering a potential route for label-free detection and classification of cancer cells by their aggressiveness.

准确和快速识别侵袭性癌细胞仍然是一个主要的临床挑战。在这里，我们提出了一个简单的、无标记的机械表型平台，该平台整合了受控的胶体地形和颗粒摄取测量，以揭示与转移进展相关的生物物理特征。通过控制沉积在细胞培养板上形成非紧密堆积的聚苯乙烯球阵列，并用薄氧化硅涂层稳定。这些阵列在不同密度下显示尺寸范围为0.23-2.3 μm的微纳米特征，并用于评估不同恶性程度癌细胞之间的粘附性。粒径大于0.5 μm时，吸附差异最为明显；粒径≥0.7 μm时，吸附差异最为明显，且随粒径增大而增大。在颗粒沉积浓度为500 μg/mL和1000 μg/mL的条件下制备胶体形貌，观察到两种条件下的粘附差异，且浓度越高效果越明显。在转移部位，细胞表现出更多的颗粒摄取，更强的粘附性和更大的胶体覆盖底物的形态接合，其特征是广泛的富含肌动蛋白的突起包裹着单个颗粒。AFM力图谱证实胶体探针具有更高的粘附力，而转录组分析显示粘附转移状态中粘附和ecm重塑途径的富集。我们还发现，淋巴选择的细胞在胶体包被表面上的粘附性降低，但与原发肿瘤细胞相比，颗粒摄取更高。这些结果表明，在离开原发肿瘤后，转移细胞的粘附潜力降低，只有在到达继发部位时才能恢复。通过暴露在平面底物上无法检测到的粘附差异，并将其与颗粒摄取测定相连接，该平台产生转移潜力的功能特征。这种方法在技术上是可行的，与成像和分子工作流程兼容，适用于高通量或临床分析，为根据癌细胞的侵袭性进行无标记检测和分类提供了一条潜在的途径。

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引用次数: 0

Fiber-integrated hydrogels: a versatile platform to improve structural and biological performance in 3D biofabrication 纤维集成水凝胶：一个多功能平台，以提高结构和生物性能的3D生物制造

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102799

Annabelle Neuhäusler , Nils Lindner , Andreas Blaeser

Hydrogels emerged as versatile biomaterials for tissue engineering due to their extra cellular matrix similarity and mechanical and biochemical properties. Still, hydrogels expose limited stiffness, anisotropy and nutrient diffusion. By reinforcing hydrogels with synthetic and natural fibers, these drawbacks can be effectively addressed, thereby enabling the modeling of advanced biomimetic tissue. This review discusses recent progress in the fabrication of fiber-integrated hydrogels and brings together developments from biomaterials, biofabrication, mechanobiology, and organ-model engineering. Fiber-addition impact on viscoelastic, time-dependent und nonlinear material properties, on multiscale and hierarchical constructs and on mechanical and biological readouts are analyzed. Specifically, the integration of both synthetic and natural fibers into hydrogel matrices is highlighted which significantly broaden their structural and biochemical versatility. These fiber-added hydrogels display improved properties including enhanced stiffness (up to 10-fold increase), anisotropy (>80 % alignment) and nutrient diffusion (4-fold increase). Moreover, the incorporation of fibers directly impacts cellular behavior by promoting adhesion, migration, proliferation and differentiation. Finally, bone, muscle and nerve tissue are exemplary presented in more detail to highlight the broad potential of these composite materials. In conclusion, fiber-embedded hydrogels represent a decisive step toward enhanced 4D-metamaterials.

水凝胶由于其细胞外基质的相似性以及机械和生化特性而成为组织工程中通用的生物材料。尽管如此，水凝胶暴露出有限的刚度、各向异性和营养扩散。通过用合成纤维和天然纤维增强水凝胶，可以有效地解决这些缺点，从而使先进的仿生组织建模成为可能。本文综述了纤维集成水凝胶制备的最新进展，并从生物材料、生物制造、机械生物学和器官模型工程等方面进行了综述。分析了纤维添加对粘弹性、时变和非线性材料性能、多尺度和分层结构以及力学和生物读数的影响。具体来说，合成纤维和天然纤维在水凝胶基质中的整合被强调，这大大拓宽了它们的结构和生化通用性。这些添加纤维的水凝胶显示出改善的性能，包括增强的刚度（增加10倍），各向异性（>； 80%对齐）和营养扩散（增加4倍）。此外，纤维的掺入通过促进粘附、迁移、增殖和分化直接影响细胞行为。最后，以骨、肌肉和神经组织为例，更详细地介绍了这些复合材料的广泛潜力。总之，纤维嵌入的水凝胶代表了增强4d超材料的决定性一步。

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引用次数: 0