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MgFe-LDH-doped GelMA hydrogel scaffold repaired spinal cord injury via immunoregulation and enhancement of neuronal differentiation mgfe - ldh掺杂GelMA水凝胶支架通过免疫调节和增强神经元分化修复脊髓损伤

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/j.nantod.2025.102944

Shasha Zheng , Ruiqi Huang , Xugang Zhuang , Qian Zhu , Qingyue Cui , Hong Cheng , Wenyu Liang , Chenyu Du , Jing Li , Bin Zhang , Xin Gao , Yusong Wang , Pan Feng , Lei Tian , Yangnan Hu , Zuhong He , Rongrong Zhu , Renjie Chai

Spinal cord injury (SCI) is a traumatic condition of the nervous system that leads to severe disability. Its poor prognosis is largely attributed to uncontrolled inflammation and the intrinsically limited regenerative capacity of the spinal cord, which together severely restrict functional recovery. Hydrogel-based scaffolds represent a prospective strategy for SCI repair, offering structural support and a conducive microenvironment for regeneration. Here, we developed a gelatin methacrylate (GM) hydrogel scaffold incorporating MgFe-layered double hydroxide (LDH) nanoparticles functionalized with brain-derived neurotrophic factor (BDNF). This multifunctional GM-BDNF-LDH scaffold enables sustained release of BDNF, which promotes neuronal survival and regeneration, while LDH contributes additional therapeutic benefits through immunomodulation and neurogenic support. In both in vivo and in vitro experiments, LDH promoted the differentiation of neural stem cells (NSCs) while suppressing the expression of M1 markers and promoting the expression of M2 markers in microglia. Furthermore, the functional scaffold significantly improved motor function restoration, inflammation suppression, and neural differentiation in rats. Together, these results demonstrate that the LDH-functionalized scaffold we proposed can simultaneously modulate the immune microenvironment and promote neuronal regeneration, offering a potential treatment strategy for SCI recovery.

脊髓损伤（SCI）是一种神经系统的创伤性疾病，可导致严重的残疾。其预后不良很大程度上归因于不受控制的炎症和脊髓固有的有限再生能力，这两者共同严重限制了功能恢复。水凝胶基支架为脊髓损伤修复提供了一种有前景的策略，它提供了结构支持和有利于再生的微环境。在这里，我们开发了一种明胶甲基丙烯酸酯（GM）水凝胶支架，该支架将mgfe层状双氢氧化物（LDH）纳米颗粒与脑源性神经营养因子（BDNF）功能化。这种多功能GM-BDNF-LDH支架能够持续释放BDNF，促进神经元存活和再生，而LDH通过免疫调节和神经原性支持提供额外的治疗益处。在体内和体外实验中，LDH促进神经干细胞（NSCs）的分化，同时抑制小胶质细胞中M1标记物的表达，促进M2标记物的表达。此外，功能性支架可显著改善大鼠的运动功能恢复、炎症抑制和神经分化。总之，这些结果表明，我们提出的ldh功能化支架可以同时调节免疫微环境和促进神经元再生，为脊髓损伤恢复提供了一种潜在的治疗策略。

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引用次数: 0

Peroxidase-catalyzed proximity labeling to survey the proteome of nanomaterial-cell interface during macropinocytosis-mediated internalization. 过氧化物酶催化近距离标记研究巨噬细胞介导内化过程中纳米材料-细胞界面的蛋白质组。

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 Epub Date: 2025-08-09 DOI: 10.1016/j.nantod.2025.102865

Yushuang Wei, Xiangyang Li, Yao Gong, Yue-Xuan Li, Jibin Guan, Bing Yuan, Yue Chen, Hong-Bo Pang

Nanomaterials often need to interact with proteins on the plasma membrane to get cross and access their intracellular targets. Therefore, to fully understand the cell entry mechanism, it is of vital importance to gain a comprehensive insight into the proteome at the interface when nanomaterials encounter the cells. Here, we reported a peroxidase-based proximity labeling method to survey the proteome at the nanoparticle (NP)-cell interface. Horseradish peroxidase (HRP) was conjugated to a variety of NPs and other ligand types while still being able to biotinylate the proteins surrounding NP (or ligand)-receptor complexes. Using two NP-based tracers for macropinocytosis (MP), which is highly relevant to NP internalization, we performed a proteomic survey and revealed the interface proteome difference between traditional and receptor-dependent MP. Moreover, our survey found that E-cadherin (CDH1), while not serving as the primary receptor, is present at the NP-cell interface and is functionally important for the cellular uptake of a wide variety of NPs. Overall, by integrating nanotechnology with proximity labeling, our study provides an approach to map the proteome of NP-cell interface for investigating the molecular mechanism of NP and macromolecule internalization into cells.

纳米材料通常需要与质膜上的蛋白质相互作用才能交叉并进入细胞内目标。因此，为了充分了解细胞进入机制，全面了解纳米材料与细胞接触时界面上的蛋白质组是至关重要的。在这里，我们报道了一种基于过氧化物酶的接近标记方法来研究纳米颗粒(NP)-细胞界面上的蛋白质组。辣根过氧化物酶（HRP）与多种NP和其他配体类型结合，同时仍然能够生物素化NP（或配体）-受体复合物周围的蛋白质。使用两种基于NP的巨噬细胞症（MP）示踪剂，研究人员进行了蛋白质组学调查，揭示了传统和受体依赖性MP之间的界面蛋白质组差异。此外，我们的研究发现，e -钙粘蛋白（CDH1）虽然不是主要受体，但存在于np -细胞界面，对细胞摄取多种np具有重要的功能。总的来说，通过纳米技术与接近标记的结合，我们的研究为研究NP和大分子内化进入细胞的分子机制提供了一种绘制NP-细胞界面蛋白质组的方法。

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引用次数: 0

Inside Back Cover - Graphical abstract TOC/TOC in double column continued from OBC if required, otherwise blank page 封底内-图解摘要TOC/TOC双栏，如果需要，从OBC继续，否则空白页

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/S1748-0132(25)00313-5

引用次数: 0

Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information 封底外-图形摘要TOC/双栏TOC/封面图例（如适用），条形码，摘要和索引信息

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/S1748-0132(25)00314-7

引用次数: 0

Expanding the druggable proteome strategies and innovations in targeted protein degradation 扩展靶向蛋白质降解的可药物蛋白质组策略和创新

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/j.nantod.2025.102945

Ke Ma , Ting Liu , Wen-Bo Huan, Ke-Zheng Chen, Sheng-Lin Qiao

Targeted Protein Degradation (TPD) emerges as a novel therapeutic strategy that selectively eliminates disease-causing proteins by harnessing endogenous degradation systems, thereby overcoming the limitations of traditional drugs in addressing “undruggable” targets. This review outlines the core molecular mechanisms and primary technical platforms of TPD, including PROTACs, molecular glues (MGs), antibody-degradation conjugates, and emerging autophagy-related strategies (LYTACs, AUTACs, ATTECs, etc.). It systematically summarizes molecular engineering advances such as linker optimization, expansion of E3 ligase resources, and environmentally responsive and multi-modular designs. Furthermore, clinical and translational research cases demonstrate TPD's application potential across oncology, neurodegenerative diseases, cardiovascular disorders, and infectious diseases. Addressing challenges such as suboptimal pharmacokinetics, delivery limitations, potential off-target effects, and industrialization hurdles, we identify critical scientific questions requiring resolution and highlight emerging directions including AI-enabled design, nanomaterial delivery, and interdisciplinary integration. Overall, TPD is propelling drug development from “functional inhibition” toward “protein clearance,” injecting new vitality into precision medicine. This paper aims to provide a systematic reference for subsequent research and clinical translation.

靶向蛋白降解（Targeted Protein Degradation， TPD）作为一种新的治疗策略出现，它通过利用内源性降解系统选择性地消除致病蛋白，从而克服了传统药物在解决“不可药物”靶标方面的局限性。本文综述了TPD的核心分子机制和主要技术平台，包括PROTACs、分子胶（MGs）、抗体降解偶联物以及新兴的自噬相关策略（lytac、autac、attec等）。系统总结了分子工程方面的研究进展，如连接子优化、E3连接酶资源拓展、环境响应和多模块化设计等。此外，临床和转化研究案例证明了TPD在肿瘤、神经退行性疾病、心血管疾病和传染病方面的应用潜力。为了解决诸如次优药代动力学、递送限制、潜在脱靶效应和工业化障碍等挑战，我们确定了需要解决的关键科学问题，并强调了新兴方向，包括人工智能设计、纳米材料递送和跨学科整合。总的来说，TPD正在推动药物开发从“功能抑制”走向“蛋白质清除”，为精准医学注入新的活力。本文旨在为后续研究和临床翻译提供系统的参考。

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引用次数: 0

Copper-doxorubicin nanodot-based dual catalytic metal prodrug liposome for enhanced chemotherapy and Chemodynamic Combination Therapychemodynamic combination therapy 基于铜-阿霉素纳米点的双催化金属前药脂质体用于强化化疗和化学动力联合治疗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-28 DOI: 10.1016/j.nantod.2025.102935

Chuanyong Fan , Yao Zhou , Yihua Mei, Kaifang Wu, Meng Wang, Limeng Chen, Hongyan Liu, Zehao Dong, Lu Xu

Although metal-based antitumor agents have for long been crucial components of most chemotherapy regimens, the majority of contemporary antitumor drugs have exhibited limited tumor selectivity and considerable off-target toxicity, restricting their therapeutic efficacy. Herein, metal prodrug nanodots (CD) comprising Cu^2 + and Doxorubicin (DOX) were first synthesized via coordination interaction. They were then co-loaded with Dihydroartemisinin (DHA) in a liposome nano-delivery system to enhance the metal drug’s selectivity and antitumor activity. The CD nanodots exhibited dual sensitivity to acid and Glutathione (GSH), which in turn, facilitated efficient tumor-specific drug release. Furthermore, the released Cu²⁺ could catalyze the endogenous H₂O₂ and loaded DHA, producing numerous toxic free radicals, which, in turn, induced lipid peroxidation and facilitated a synergistic antitumor effect of both Chemodynamic Therapy (CDT) and conventional chemotherapy. At the same time, Cu²⁺ decreased the GSH-mediated scavenging effect on the produced Reactive Oxygen Species (ROS) via a redox reaction, further enhancing the lethal effect of ROS on tumor cells. Given its potential clinical utility, this metal prodrug strategy could be leveraged for a safe and effective treatment of tumors.

虽然金属基抗肿瘤药物长期以来一直是大多数化疗方案的重要组成部分，但大多数当代抗肿瘤药物表现出有限的肿瘤选择性和相当大的脱靶毒性，限制了它们的治疗效果。本文首次通过配位相互作用合成了由Cu2 +和阿霉素（DOX）组成的金属药前纳米点（CD）。然后在脂质体纳米递送系统中与双氢青蒿素（DHA）共载，以增强金属药物的选择性和抗肿瘤活性。CD纳米点对酸和谷胱甘肽（GSH）具有双重敏感性，从而促进了肿瘤特异性药物的有效释放。此外，释放的Cu2+可以催化内源性H2O2和负载的DHA，产生大量有毒自由基，从而诱导脂质过氧化，促进CDT和常规化疗的协同抗肿瘤作用。同时，Cu2+降低了gsh对氧化还原反应产生的活性氧（Reactive Oxygen Species， ROS）的清除作用，进一步增强了ROS对肿瘤细胞的杀伤作用。鉴于其潜在的临床应用，这种金属前药策略可以用于安全有效的肿瘤治疗。

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引用次数: 0

ROS/NO dual-releasing organic polymer nanoenzymes for NIR-II photo-adjuvant cancer immunotherapy ROS/NO双释放有机聚合物纳米酶用于NIR-II光辅助癌症免疫治疗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-25 DOI: 10.1016/j.nantod.2025.102936

Jiayao Ding , Long Wang , Fengshuo Wang , Yue Liu , Haidong Chen , Jingchao Li , Ting Su

Nitric oxide (NO) and reactive oxygen species (ROS) are crucial signal molecules in living systems, providing alternative strategies for cancer treatment other than chemotherapy drug. Nevertheless, the uncontrollable ROS/NO induction will lead to low therapeutic results and potential off-target effects. In this paper, ROS/NO dual-releasing organic polymeric nanoenzymes (O₂^·-/NO-SPN) are designed, capable of synergistically elevating ROS and NO levels in tumors upon second near-infrared (NIR-II) photo-triggered activation, thus establishing a photoactivated adjuvant strategy for enhanced cancer immunotherapy. A newly synthesized semiconducting polymer (L7) with an outstanding NIR-II photothermal performance is utilized as the core for fabricating such nanoenzymes. Using a film-dispersion technique coupled with hydration, a NO donor S-nitrosoglutathione (GSNO), superoxide anions (O₂^·-) donor 3-indoleacetic acid (3IAA) and L7 are co-loaded in a thermal-responsive nano-liposome, followed by surface embellishment of horseradish peroxidase (HRP). The formed O₂^·-/NO-SPN can generate local heat via NIR-II photothermal effect, and thus the thermal-responsive nano-liposomes are collapsed to release 3IAA, which is then catalyzed by HRP to produce O₂^·-, triggering tumor cell death in a NIR-II photodynamic-like manner. Moreover, the local heating effect results in production of NO by GSNO to further kill tumor cells and also activate the systemic immune responses through inducing immunogenic cell death and macrophage polarization. This ROS/NO dual-releasing strategy is demonstrated to effectively inhibit bilateral tumor growths and metastasis. The current study thereby offers a promising tool to regulate both ROS and NO levels concurrently in biological systems.

一氧化氮（NO）和活性氧（ROS）是生命系统中至关重要的信号分子，为癌症治疗提供了化疗药物以外的替代策略。然而，不可控的ROS/NO诱导将导致低治疗效果和潜在的脱靶效应。本文设计了ROS/NO双释放有机聚合物纳米酶（O2·-/NO- spn），在第二次近红外（NIR-II）光触发激活下，能够协同提高肿瘤中ROS和NO的水平，从而建立了一种增强癌症免疫治疗的光激活佐剂策略。一种新合成的半导体聚合物（L7）具有优异的NIR-II光热性能，被用作制造这种纳米酶的核心。利用膜分散技术和水合作用，将NO供体s -亚硝基谷胱甘肽（GSNO）、超氧阴离子（O2·-）供体3-吲哚乙酸（3IAA）和L7共负载在热响应的纳米脂质体中，然后在表面修饰辣根过氧化物酶（HRP）。形成的O2·-/NO-SPN通过NIR-II光热效应产生局部热量，热响应的纳米脂质体被分解释放3IAA， 3IAA被HRP催化生成O2·-，以类似NIR-II光动力学的方式触发肿瘤细胞死亡。此外，局部加热效应导致GSNO产生NO进一步杀伤肿瘤细胞，并通过诱导免疫原性细胞死亡和巨噬细胞极化激活全身免疫反应。这种ROS/NO双释放策略被证明能有效抑制双侧肿瘤的生长和转移。因此，目前的研究提供了一种有前途的工具来同时调节生物系统中的ROS和NO水平。

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引用次数: 0

Corrigendum to “Real-time ROS monitoring-guided tumor electrodynamic therapy using a metal microneedle array system” [Nano Today 63 (2025) 102731] “使用金属微针阵列系统的实时ROS监测引导肿瘤电动力治疗”的勘误表[Nano Today 63 (2025) 102731]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-20 DOI: 10.1016/j.nantod.2025.102933

Xiaoxue Xie , Jing Liu , Zhengjie Liu , Huiye Wei , Minzhao Lin , Gengjia Chen , Zhibo Liu , Mengyi He , Xinshuo Huang , Shuang Huang , Yunuo Wang , Ji Wang , Huijiuan Chen , Qi Chen , Xi Xie , Xintao Shuai

引用次数: 0

Integrated DNA logic gate-driven cell membrane confined amplification system for imaging cellular events 集成DNA逻辑门驱动的细胞膜限制扩增系统，用于细胞事件成像

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-20 DOI: 10.1016/j.nantod.2025.102934

Zhenzhen Guo , Yue Qiu , Yang Wang , Jiali Zhang , Xiaotong Jiang , Danyu Wang , Hua Yi , Mengyu Huang , Peiru Chen , Fangmei Zhang , Yan Liang , Fengming Chen , Hua Gao , Qiuxia Yang , Kaixiang Zhang

The spatiotemporal profiling of membrane-localized biomarkers of cellular events is pivotal for unraveling disease pathogenesis and advancing precision medicine. However, the current inefficient multi-target discrimination, due to the limited computational capacity of monovalent logic elements and diffusion-limited signal amplification strategies, has hindered its advancement. Here, we present an innovative platform that enables integrated DNA logic gate-driven, spatially confined signal amplification at membrane interfaces. In the design, by encoding traditional monovalent DNA logic units into multivalent tandem architectures, we developed next-generation integrated DNA logic gate elements (iLGE), enabling parallel Boolean operations on multiple biomarkers with threefold enhanced computation efficiency and reduced spatial dependency. Additionally, embedding DNAzyme-mediated signal switches and substrates within a multivalent amphiphilic DNA scaffold enabled the engineering of a DNA walker device (DWD) that stably anchors to the cell membrane, facilitating a dual spatially confined signal amplification strategy. This platform possesses high sensitivity and precision in detecting localized nucleic acids, proteins, and specific cells at the engineered cell membrane interface, thereby enabling precise capture and analysis of events, including cell damage, cellular oncogenesis, and interactions between NK cells and tumor cells. It offers a new, comprehensive diagnostic and analytical platform for exploring membrane-localized events and their related disease mechanisms.

细胞事件的膜定位生物标志物的时空特征分析对于揭示疾病发病机制和推进精准医学至关重要。然而，目前由于单价逻辑元件的计算能力有限和限制扩散的信号放大策略，多目标识别效率低下，阻碍了多目标识别技术的发展。在这里，我们提出了一个创新的平台，可以在膜界面上集成DNA逻辑门驱动的空间受限信号放大。在设计中，通过将传统的单价DNA逻辑单元编码为多价串联架构，我们开发了下一代集成DNA逻辑门元件（iLGE），实现了对多个生物标志物的并行布尔运算，提高了三倍的计算效率，降低了空间依赖性。此外，将dnazyme介导的信号开关和底物嵌入多价两亲性DNA支架中，可以实现DNA行走装置（DWD）的工程设计，该装置可以稳定地锚定在细胞膜上，促进双重空间受限的信号放大策略。该平台在检测工程细胞膜界面的局部核酸、蛋白质和特定细胞方面具有很高的灵敏度和精度，从而能够精确捕获和分析事件，包括细胞损伤、细胞肿瘤发生以及NK细胞与肿瘤细胞之间的相互作用。它为探索膜定位事件及其相关疾病机制提供了一个新的、全面的诊断和分析平台。

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引用次数: 0

Corrigendum to “Sonodynamic biodegradable pseduo-conjugate polymer delivery of warfarin for inducing generation of cancerous ROS and ferroptosis” [Nano Today 66 (2026) 102891] “声动力可生物降解伪共轭聚合物递送华法林诱导产生癌变ROS和铁下垂”的勘误表[纳米今日66 (2026)102891]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-19 DOI: 10.1016/j.nantod.2025.102928

Pengchen Wang , Jintong Na , Xiyu Liu , Minhui Cui , Ganghao Liang , Xinyue He , Haihua Xiao , Yongxiang Zhao , Yuan Liao , Liping Zhong

引用次数: 0

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