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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 : 2026-02-01 Epub 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

Revolutionizing role of magnetic field-guided MnFe2O4@ZIF-8@retinoic acid in DUCA conduits for inflammation inhibition and peripheral nerve regeneration 革命性的作用磁场引导MnFe2O4@ZIF-8@维甲酸在DUCA导管炎症抑制和周围神经再生

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2025-09-30 DOI: 10.1016/j.nantod.2025.102910

Majid Sharifi , Majid Salehi , Somayeh Ebrahimi-Barough , Mohammad Kamalabadi-Farahani

Neuroma formation following the repair of nerve injuries exceeding 0.9 cm in length severely impedes functional recovery. To overcome this challenge, we engineered magnetically responsive core-shell nanoparticles (MnFe₂O₄@ZIF-8@Retinoic acid, MFZR; 90–360 nm) to guide regeneration within a decellularized umbilical cord artery (DUCA) conduit. We investigated the synergistic effect of MFZR under an external magnetic field (MF) on Schwann cell behavior in vitro and on sciatic nerve repair in a rat model. Under MF exposure, MFZR significantly enhanced Schwann cell migration, alignment, and elongation on DUCA conduits. In-vivo, the MFZR+MF combination potently promoted functional recovery, as measured by the sciatic functional index, muscle compound action potential, and nerve conduction velocity, without inducing DUCA-related inflammation. Histological analysis demonstrated robust regeneration, characterized by increased axon diameter, an improved G-ratio, and elevated expression of S100 and NF-200. This regeneration was facilitated by a healing-promoting M2 macrophage polarization at the injury site. Critically, the strategy exhibited no systemic toxicity. These findings establish that magnetically guided MFZR effectively prevents neuroma in the DUCA conduits, orchestrates a pro-regenerative microenvironment, and achieves significant functional recovery, offering a promising translatable strategy for nerve repair.

长度超过0.9 cm的神经损伤修复后形成的神经瘤严重阻碍功能恢复。为了克服这一挑战，我们设计了磁响应核壳纳米颗粒（MnFe2O4@ZIF-8@维甲酸，MFZR; 90-360 nm）来引导去细胞脐带动脉（DUCA）导管内的再生。我们研究了外磁场作用下MFZR对体外雪旺细胞行为和大鼠坐骨神经修复的协同作用。在中频暴露下，MFZR显著增强了DUCA导管上雪旺细胞的迁移、排列和伸长。在体内，通过坐骨功能指数、肌肉复合动作电位和神经传导速度测量，MFZR+MF联合有效促进功能恢复，而不会引起duca相关炎症。组织学分析显示再生强劲，其特征是轴突直径增加，g比改善，S100和NF-200表达升高。损伤部位促进愈合的M2巨噬细胞极化促进了这种再生。关键的是，该策略没有表现出系统性毒性。这些发现表明，磁引导MFZR有效地预防了DUCA导管中的神经瘤，协调了一个促进再生的微环境，并实现了显著的功能恢复，为神经修复提供了一种有前途的可翻译策略。

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引用次数: 0

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 : 2026-02-01 Epub 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

Mannosylated siRNA/PERKi nanoassemblies reprogram macrophages to block tumor metastasis 甘露糖基化siRNA/PERKi纳米组件重编程巨噬细胞以阻止肿瘤转移

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2026-01-14 DOI: 10.1016/j.nantod.2026.102975

Junjie Ren , Shiyin Zhao , Dali Wang , Yao Wang , Wei Huang , Feng Zhu , Lijuan Zhu , Deyue Yan

Tumor-associated macrophages (TAMs) are pivotal mediators of the immunosuppressive tumor microenvironment (TME), promoting immune evasion and tumor progression. Current TAM-targeted therapies, which aim to repolarize immunosuppressive M2-polarized TAMs into tumoricidal M1 phenotype, face limitations due to the complex immunosuppressive networks within the TME. To address this challenge, we developed a mannosylated nanodrug for TAM targeting through the co-assembly of an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERKi) and mannoseylated PD-L1 siRNA (Man-siPDL1). This dual-targeting nanodrug simultaneously disrupts PERK-mediated immunosuppression and PD-L1 checkpoint signaling, effectively inducing M2-to-M1 repolarization and enhancing cytotoxic T lymphocytes (CTLs) infiltration. In Hepa1–6 tumor models, the mannosylated nanodrug demonstrated superior tumor targeting and TME remodelling, evidenced by an increased M1/M2 TAM ratio, elevated CTLs populations, superior PD-L1 downregulation, and enhanced immunostimulatory cytokine expression. This strategy not only overcomes key immunosuppressive barriers in solid tumors but also provides a versatile platform for RNAi-based immunotherapy, with potential applications across diverse cancer types.

肿瘤相关巨噬细胞（tam）是免疫抑制肿瘤微环境（TME）的关键介质，促进免疫逃避和肿瘤进展。目前的tam靶向治疗旨在将免疫抑制的m2极化tam重新极化为杀肿瘤的M1表型，由于TME内复杂的免疫抑制网络而面临局限性。为了解决这一挑战，我们通过蛋白激酶rna样内质网激酶（PERKi）抑制剂和甘露糖化PD-L1 siRNA （Man-siPDL1）的共组装，开发了一种针对TAM的甘露糖化纳米药物。这种双靶向纳米药物同时破坏perk介导的免疫抑制和PD-L1检查点信号，有效诱导m2到m1再极化并增强细胞毒性T淋巴细胞（ctl）浸润。在Hepa1-6肿瘤模型中，甘糖基化纳米药物表现出优越的肿瘤靶向性和TME重塑，证明了M1/M2 TAM比例增加、ctl数量增加、PD-L1下调和免疫刺激细胞因子表达增强。该策略不仅克服了实体肿瘤中关键的免疫抑制屏障，而且为基于rnai的免疫治疗提供了一个多功能平台，在不同类型的癌症中具有潜在的应用前景。

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引用次数: 0

Repurposing ferumoxytol as a nanowarming agent for vitrification-based organ preservation 阿魏木醇作为纳米暖化剂用于玻璃化器官保存的研究

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2026-01-16 DOI: 10.1016/j.nantod.2026.102981

Haikao Feng , Yu Mao , Yaolong Zhang , Guangxiang Si , Kun Lu , Ming Zheng , Weijie Ni , Yan Li , Yingyu Huang , Miao Zhang , Ning Gu

Organ vitrification, a cryopreservation technique achieved by vascular perfusion of cryoprotective agents (CPAs) and rapid cooling to a stable glass-like state, enables long-term organ preservation in cryogenic state. However, rewarming vitrified organs to a transplantable state remains a major challenge, as it requires rapid and uniform heating to prevent ice recrystallization and mechanical cracking. Nanowarming, which exploits the heat-generating properties of iron oxide nanoparticles (IONPs) under an alternating magnetic field (AMF), has been shown to enable successful recovery of vitrified organs through vascular perfusion and AMF-induced homogeneous warming. Yet, the potential use of clinically approved IONPs, such as Ferumoxytol, in nanowarming has not been investigated. Here, we report pivotal studies on the vitrification and nanowarming of rat kidneys using Ferumoxytol. Our findings demonstrate that Ferumoxytol remains highly stable in CPAs, enables a ∼10-fold faster warming rate (∼79.9 °C/min) than the cooling rate (∼8.0 °C/min), and produces uniform warming kinetics across the cortex, medulla, and hilum of rat kidneys. Importantly, vitrified kidneys recovered by Ferumoxytol-based nanowarming exhibited comparable viability to both fresh controls and static cold stored kidneys, as assessed by renal pathology and vascular endothelium staining. Given its established clinical use as an iron supplement and MRI contrast agent, Ferumoxytol may serve as a readily translatable nanowarming agent, potentially accelerating the clinical adoption of organ vitrification and nanowarming.

器官玻璃化是一种低温保存技术，通过血管灌注冷冻保护剂（cpa）并快速冷却到稳定的玻璃状状态，可以在低温状态下长期保存器官。然而，将玻璃化的器官重新加热到可移植状态仍然是一个主要挑战，因为它需要快速和均匀的加热，以防止冰再结晶和机械开裂。纳米增温利用了氧化铁纳米颗粒（IONPs）在交变磁场（AMF）下的发热特性，已被证明能够通过血管灌注和AMF诱导的均匀增温成功恢复玻璃化器官。然而，临床批准的离子内酯（IONPs），如阿鲁莫木糖醇，在纳米变暖中的潜在用途尚未得到研究。在这里，我们报告了使用阿魏木醇玻璃化和纳米加热大鼠肾脏的关键研究。我们的研究结果表明，阿魏木糖醇在CPAs中保持高度稳定，使升温速率（~ 79.9 °C/min）比冷却速率（~ 8.0 °C/min）快~ 10倍，并在大鼠肾脏皮质、髓质和肾门产生均匀的升温动力学。重要的是，通过肾脏病理学和血管内皮染色评估，阿魏木酚纳米加热恢复的玻璃化肾脏与新鲜对照和静态冷藏肾脏的活力相当。鉴于其作为铁补充剂和MRI造影剂的临床应用，阿魏木醇可能作为一种易于翻译的纳米暖化剂，可能加速器官玻璃化和纳米暖化的临床应用。

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引用次数: 0

Nanomedicine strategies for enhancing calcium overload in cancer therapy: A focus on regulating cellular function 在癌症治疗中增强钙超载的纳米药物策略：聚焦于调节细胞功能

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2025-11-10 DOI: 10.1016/j.nantod.2025.102927

Jingyu Li , Dan Shi , Bin Wang , Mengru Li , Qiwei Tian , Wei Wei

Calcium(Ca²⁺) overload, defined by excessive intracellular calcium levels that trigger apoptosis or necrosis—particularly in tumor cells—has emerged as a promising ion interference strategy in cancer therapy. However, tumor cells often evade apoptosis through the regulation of calcium channels and transporters, limiting the effectiveness of conventional Ca²⁺ delivery methods. To address this, nanomedicine-based strategies combined with cell function regulation have been developed to disrupt Ca²⁺ homeostasis in tumor cells by increasing Ca²⁺ influx or inhibiting efflux. These strategies employ nanomedicine to increase extracellular calcium concentration([Ca²⁺]ext), open calcium channels, or inhibit calcium efflux via specific channel and transporter blockers, leading to sustained elevation of the intracellular calcium concentration([Ca²⁺]int). This review systematically examines Ca²⁺ regulatory mechanisms in tumor cells and evaluates diverse strategies to amplify the therapeutic potential of Ca²⁺ overload. Through this analysis, we offer insights for advancing the development of Ca²⁺ overload as a targeted approach in cancer treatment.

钙（Ca 2 +）超载，定义为细胞内钙水平过高，触发细胞凋亡或坏死，特别是在肿瘤细胞中，已经成为癌症治疗中有前途的离子干扰策略。然而，肿瘤细胞经常通过钙通道和转运体的调节来逃避细胞凋亡，这限制了传统Ca 2 +递送方法的有效性。为了解决这个问题，已经开发出基于纳米药物的策略，结合细胞功能调节，通过增加Ca 2 +内流或抑制外排来破坏肿瘤细胞中Ca 2 +的稳态。这些策略使用纳米药物增加细胞外钙浓度（[Ca 2 +]外），打开钙通道，或通过特定通道和转运蛋白阻滞剂抑制钙外排，导致细胞内钙浓度持续升高（[Ca 2 +]外）。这篇综述系统地研究了Ca 2 +在肿瘤细胞中的调节机制，并评估了多种策略来扩大Ca 2 +过载的治疗潜力。通过这一分析，我们为推进ca2 +过载作为癌症治疗的靶向方法的发展提供了见解。

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引用次数: 0

Antifouling zwitterionic coating enhances electrochemical aptamer-based sensors for therapeutic drug monitoring 防污两性离子涂层增强了用于治疗药物监测的电化学适体传感器

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2025-09-16 DOI: 10.1016/j.nantod.2025.102892

Haowei Duan , Shuhua Peng , Shuai He , Shi-Yang Tang , Keisuke Goda , Chun H. Wang , Ming Li

Electrochemical aptamer-based (E-AB) sensors have experienced remarkable growth across a broad range of applications, such as precision medicine, chronic disease management, food safety, and environmental monitoring, due to their exceptional capability for real-time and continuous monitoring of biomarkers. However, biofouling in complex biological environments remains a critical challenge for the E-AB sensors, compromising signal strength, operational stability, and biosensing specificity. Here, we present a zwitterionic coating strategy that integrates poly-sulfobetaine methacrylate (SBMA) and polydopamine (PDA) to enhance the antifouling properties of the E-AB sensors, thereby enabling sensitive, stable, and accurate detection of a model antibiotic drug, vancomycin. The durable and hydrophilic antifouling layer was grafted onto the electrode surface to minimize signal drift while preserving sufficient signal on the E-AB sensors. The SBMA@PDA coating was systematically optimized and demonstrated superior resistance to biofouling under various environmental conditions, including pH, temperature, and mechanical stress. Furthermore, the coating was incorporated into a wearable microneedle patch for monitoring vancomycin dynamics in artificial interstitial fluids, achieving robust stability and performance. These findings establish a reliable and effective antifouling approach, advancing the practical application of E-AB sensors for continuous therapeutic drug monitoring in clinical and wearable healthcare settings.

基于电化学适配体（E-AB）的传感器由于具有实时和连续监测生物标志物的卓越能力，在精准医疗、慢性疾病管理、食品安全和环境监测等广泛应用中取得了显着增长。然而，复杂生物环境中的生物污垢仍然是E-AB传感器面临的一个关键挑战，它会影响信号强度、运行稳定性和生物传感特异性。在这里，我们提出了一种两性离子涂层策略，该策略集成了聚甲基丙烯酸磺基甜菜碱（SBMA）和聚多巴胺（PDA），以增强E-AB传感器的防污性能，从而实现对模型抗生素万古霉素的敏感、稳定和准确检测。在电极表面接枝了耐用且亲水的防污层，以减少信号漂移，同时保持E-AB传感器上足够的信号。对SBMA@PDA涂层进行了系统优化，并在各种环境条件下（包括pH、温度和机械应力）表现出优异的抗生物污染能力。此外，该涂层被纳入可穿戴微针贴片中，用于监测人工间质液中万古霉素的动态，获得了强大的稳定性和性能。这些发现建立了一种可靠有效的防污方法，推进了E-AB传感器在临床和可穿戴医疗保健环境中持续治疗药物监测的实际应用。

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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 : 2026-02-01 Epub 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

Engineered nanovesicles amplify the crosstalk between neurogenesis and angiogenesis for pro-regenerative niche construction 工程纳米囊泡放大神经发生和血管生成之间的串扰，促进再生生态位的构建

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2025-11-18 DOI: 10.1016/j.nantod.2025.102932

Chengheng Wu , Zhihong Chen , Jialu Li , Rong Li , Wei Zhang , Yusheng Zhang , Gaowei Li , Peng Liu , Fuheng Hu , Kunlun Ding , Jie Ding , Dan Wei , Jing Sun , Xiaoyin Liu , Liangxue Zhou , Hongsong Fan

Nano-structured derivatives of natural organisms are enabling advances in biomaterial design, offering an innovative strategy to endow materials with specific biofunctions. In the regeneration of nervous tissue, neurogenesis and angiogenesis are intricately linked processes, yet their crosstalk in therapeutic strategies remains underexplored. This study develops an approach to produce engineered nanovisicles by pre-conditioning neural stem cells (NSCs) with brain-derived neurotrophic factor (BDNF). Compared with naive NSC exosomes, BDNF-preconditioned NSC exosomes (BNE) exhibited presented altered miRNA profiles enriched in pathways regulating neurogenesis, angiogenesis, and inflammation. In vitro assays demonstrated that BNE significantly enhanced NSC migration, neuronal/oligodendrocytic differentiation, and neuronal maturation, while promoting human umbilical vein endothelial cell (HUVEC) migration, invasion, and angiogenesis. Critically, a coculture system confirmed bidirectional crosstalk between neurogenesis and angiogenesis, which was amplified by the BNE. In a rat traumatic brain injury (TBI) model, the BNE-laden hydrogel synergistically mitigated neuroinflammation, recruited endogenous neural stem/progenitor cells (NSPCs) to the lesion, enhanced their neuronal differentiation and maturation, and stimulated angiogenesis. This pro-regenerative microenvironment, facilitated by neurovascular crosstalk, led to significant neural network reconstruction, tissue restoration, and improved functional recovery. These findings establish BDNF-preconditioned NSC exosomes delivered via a biomimetic hydrogel as a potent platform for CNS repair, harnessing the critical crosstalk between neurogenesis and angiogenesis.

天然生物的纳米结构衍生物正在推动生物材料设计的进步，为赋予材料特定的生物功能提供了一种创新策略。在神经组织再生中，神经发生和血管生成是错综复杂的相互关联的过程，但它们在治疗策略中的相互作用仍未得到充分探讨。本研究开发了一种利用脑源性神经营养因子（BDNF）预处理神经干细胞（NSCs）产生工程化纳米可见体的方法。与未处理的NSC外泌体相比，bdnf预处理的NSC外泌体（BNE）显示出改变的miRNA谱，这些miRNA谱在调节神经发生、血管生成和炎症的途径中富集。体外实验表明，BNE显著增强NSC迁移、神经元/少突胶质细胞分化和神经元成熟，同时促进人脐静脉内皮细胞（HUVEC）迁移、侵袭和血管生成。重要的是，共培养系统证实了神经发生和血管生成之间的双向串扰，这种串扰被BNE放大。在大鼠创伤性脑损伤（TBI）模型中，负载bne的水凝胶可协同减轻神经炎症，将内源性神经干/祖细胞（NSPCs）募集到病变部位，增强其神经元分化和成熟，并刺激血管生成。这种促进再生的微环境，在神经血管串扰的促进下，导致了显著的神经网络重建、组织修复和功能恢复。这些发现表明，通过仿生水凝胶递送bdnf预处理的NSC外泌体作为中枢神经系统修复的有效平台，利用了神经发生和血管生成之间的关键串串。

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引用次数: 0

18F-labeled ultrasmall nanoparticle probe for long-term PET tracking and real-time quantitative analysis of transplanted T lymphocytes in situ based on bioorthogonal reaction 基于生物正交反应的18f标记的超小纳米颗粒探针用于移植T淋巴细胞的长期PET跟踪和实时原位定量分析

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2026-02-01 Epub Date: 2025-09-11 DOI: 10.1016/j.nantod.2025.102896

Yang Chen , Wangxi Hai , Xiao Bao , Chuyi Liu , Yang Yang , Yuetan Chen , Kang Sun , Yunxuan Zhang , Ningshuang Ye , Sanyuan Shi , Samuel Kesse , Biao Li , Yuhong Xu , Jinliang Peng

The real-time, accurate understanding of the biodistribution of transplanted therapeutic cells is critical for their development and application. Positron emission tomography (PET) imaging has the potential to realize the noninvasive and quantitative evaluation of the spatial-temporal distribution of transplanted cells due to its unlimited tissue-penetration depth and quantitative capabilities, but its utility is limited by various shortcomings of existing imaging strategies or probes, such as the short half-life of the commonly used radioisotope fluorine-18 (¹⁸F) and the interference of high nonspecific background signals to the exact localization and quantification of target cells. Here, we describe a new strategy for the long-term PET tracking and real-time quantitative analysis of transplanted cells based on a tetrazine-bearing, ¹⁸F-labeled ultrasmall rare-earth nanoparticle probe (Tz-[¹⁸F]NaGdF₄) capable of labeling trans-cyclooctene (TCO) pretagged T lymphocytes via a bioorthogonal reaction at any point after their transplantation. The ultrasmall Tz-[¹⁸F]NaGdF₄ is readily prepared and characterized by rapid renal clearance and low nonspecific accumulation in major organs. The specific reaction between the Tz-[¹⁸F]NaGdF₄ probe and pretagged cells under physiological conditions enabled the specific PET imaging of target cells with low background in situ, and the measured PET image-derived standardized uptake value linearly and positively correlated with the number of pretagged T lymphocytes retained in tissues, ensuring their accurate quantification based on real-time PET signals. Therefore, the bioorthogonal reaction-based Tz-[¹⁸F]NaGdF₄-PET represents a useful tool for the long-term tracking and real-time quantification of transplanted cells in vivo.

实时、准确地了解移植治疗细胞的生物分布对其开发和应用至关重要。正电子发射断层扫描（PET）成像由于其无限的组织穿透深度和定量能力，有可能实现移植细胞时空分布的无创定量评估，但其实用性受到现有成像策略或探针的各种缺点的限制。例如常用的放射性同位素氟-18 （18F）的半衰期短，以及高非特异性背景信号对目标细胞精确定位和定量的干扰。在这里，我们描述了一种新的策略，用于移植细胞的长期PET跟踪和实时定量分析，该策略基于含四氮，18F标记的超小稀土纳米颗粒探针（Tz-[18F]NaGdF4），能够在移植后的任何时间点通过生物正交反应标记反式环烯（TCO）预标记的T淋巴细胞。超小Tz-[18F]NaGdF4易于制备，具有肾清除快、主要器官非特异性蓄积低的特点。Tz-[18F]NaGdF4探针与预标记细胞在生理条件下的特异性反应，使得低背景下靶细胞的原位特异性PET成像得以实现，测得的PET图像衍生的标准化摄取值与组织中保留的预标记T淋巴细胞数量呈线性正相关，确保了基于实时PET信号的准确定量。因此，基于生物正交反应的Tz-[18F]NaGdF4-PET是长期跟踪和实时定量体内移植细胞的有用工具。

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引用次数: 0