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Rational design of extracellular vesicles for targeted drug delivery across physiological barriers 合理设计细胞外囊泡以跨越生理屏障靶向药物递送

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-01 DOI: 10.1016/j.nantod.2025.102920

Helna M. Baby , Hengli Zhang , Andrew Selvadoss , Tanvi V. Pathrikar , Ambika G. Bajpayee

Extracellular vesicles (EVs) are naturally secreted, non-nuclear lipid nanostructures by biological sources with intrinsic features such as biocompatibility, low immunogenicity, and the ability to bypass biological barriers. Despite the growing interest in EV research, their biological potential as a versatile drug delivery vehicle has yet to be widely translated for clinical use. Fewer than 3 % of clinical trials involving these cell-free vesicles have utilized them for drug delivery applications. This review elucidates the reasons behind the translational gap through a comprehensive analysis of pharmacokinetic and tissue transport challenges faced by EVs across various tissue barriers, including the cartilage, blood-brain interface, ocular, gastrointestinal, and skin tissues, and summarizes their endogenous roles within these tissue microenvironments. The review also delves into key engineering design principles, presenting a portfolio of both tissue-specific and tissue-independent targeting strategies to overcome tissue barriers and enhance the precise delivery of engineered EVs. A comprehensive comparison of key factors – such as biodistribution, cellular uptake, intracellular fate, and safety profile – between EVs and benchmark synthetic platforms is also provided to guide the selection of optimal carrier designs for diverse tissue targets and further highlights the steps needed to bridge translational gaps of engineered EVs from a clinical perspective. In conclusion, the review underscores the significance of engineered EVs as a promising next-generation nanocarrier for precision nanomedicine, offering an alternative to conventional synthetic platforms.

细胞外囊泡（EVs）是由生物来源自然分泌的非核脂质纳米结构，具有生物相容性、低免疫原性和绕过生物屏障的能力等固有特征。尽管对EV研究的兴趣日益浓厚，但其作为多功能药物传递载体的生物学潜力尚未广泛转化为临床应用。在涉及这些无细胞囊泡的临床试验中，利用它们进行药物输送的比例不到3% %。本文通过对ev在各种组织屏障（包括软骨、血脑界面、眼、胃肠道和皮肤组织）中所面临的药代动力学和组织运输挑战的综合分析，阐明了翻译差距背后的原因，并总结了它们在这些组织微环境中的内源性作用。该综述还深入探讨了关键的工程设计原则，提出了一系列组织特异性和组织无关的靶向策略，以克服组织障碍，提高工程电动汽车的精确交付。本文还对电动汽车和基准合成平台之间的关键因素（如生物分布、细胞摄取、细胞内命运和安全性）进行了全面比较，以指导针对不同组织靶点的最佳载体设计的选择，并进一步强调了从临床角度弥合工程电动汽车翻译差距所需的步骤。总之，该综述强调了工程化电动汽车作为精密纳米医学的下一代纳米载体的重要性，为传统合成平台提供了一种替代方案。

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引用次数: 0

Silico-driven drug discovery: A paradigm shift for nanomedicine science and industry 硅驱动的药物发现：纳米医学科学和工业的范式转变

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-28 DOI: 10.1016/j.nantod.2025.102918

Yadong Jin , Yiting Zhou , Zhuo Xu , Zhifei Jin , Huan Meng , Suping Li , Liang Yan , Hui Wang , Jia-Jia Zheng , Xingfa Gao , Yuliang Zhao

The integration of artificial intelligence (AI) into drug discovery has evolved from early computer-aided design to advanced AI-driven methodologies, laying the foundation for a transformative paradigm: Silico-driven Drug Discovery (SDD). Unlike conventional approaches where AI supports isolated stages, SDD treats the entire research process, including literature understanding, hypothesis generation, molecular design, and experimental validation, as a unified, potentially autonomous system. This review proposes the THINK–BUILD–OPERATE (TBO) architecture as a universal framework for implementing SDD and outlines its six-level automation pathway from human-led to fully autonomous discovery. We highlight nanomedicine as an optimal frontier for SDD due to its well-defined theoretical foundations, abundant multi-omics and pharmacological data, and supportive regulatory shifts. By integrating domain-specific toolchains, large-scale AI models, and orchestrated self-driving laboratories, SDD can accelerate complex, multidisciplinary research while reducing costs and timelines. We further identify key challenges including AI model reliability, infrastructure interoperability, and automated laboratory versatility that must be addressed to achieve this vision. Ultimately, the convergence of AI, advanced laboratory automation, and global research networking holds the potential to transform drug discovery into an industrial-scale, programmable scientific enterprise.

人工智能（AI）与药物发现的整合已经从早期的计算机辅助设计发展到先进的人工智能驱动方法，为一种变革性范式奠定了基础：硅驱动药物发现（SDD）。与人工智能支持孤立阶段的传统方法不同，SDD将整个研究过程（包括文献理解、假设生成、分子设计和实验验证）视为一个统一的、潜在的自治系统。本文提出了THINK-BUILD-OPERATE （TBO）架构作为实现SDD的通用框架，并概述了其从人类主导到完全自主发现的六级自动化路径。由于其明确的理论基础、丰富的多组学和药理学数据以及支持性的调控转变，我们强调纳米医学是SDD的最佳前沿。通过集成特定领域的工具链、大规模人工智能模型和精心安排的自动驾驶实验室，SDD可以加速复杂的多学科研究，同时降低成本和时间。我们进一步确定了实现这一愿景必须解决的关键挑战，包括人工智能模型可靠性、基础设施互操作性和自动化实验室的多功能性。最终，人工智能、先进实验室自动化和全球研究网络的融合有可能将药物发现转变为工业规模、可编程的科学企业。

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引用次数: 0

Corrigendum to “A dual-cell-targeting epigenetic nano-editor for reshaping the intratumoral T cell niche” [Nano Today 65 (2025), 102842] “用于重塑肿瘤内T细胞生态位的双细胞靶向表观遗传纳米编辑器”的更正[Nano Today 65 (2025), 102842]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-27 DOI: 10.1016/j.nantod.2025.102922

Wenyan She , Pengdi Zhang , Linlin Guo , Yu Zhang , Haoyi Zhu , Yaping Wang , Yichao Zheng , Lin Hou

引用次数: 0

Self-assembled peptide nanofibrous hydrogel based multifunctional platform for rapid reprogramming and in situ monitoring of tumor cells into cancer stem cells 基于自组装肽纳米纤维水凝胶的多功能平台快速重编程和原位监测肿瘤细胞转化为癌症干细胞

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-25 DOI: 10.1016/j.nantod.2025.102921

Xue Wei , Mingxuan Hao , Hanzhi Xiong , Zufa Sabeel , Wenjing Zhang , Yan Liu , Yunfan Zhou , Zhao Yang , Xu Chen , Wensheng Yang

Cancer stem cells (CSCs), inherently resistant to chemotherapy and radiotherapy, are key drivers of tumor recurrence and metastasis. Conventional in vitro CSC enrichment models relying on tumor isolation and sphere-formation are often time-consuming and inefficient. Meanwhile, the separation and characterization of CSC face challenges. Here, a self-assembled peptide nanofibrous hydrogel-based multifunctional platform composed of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) serves as a functional 3D matrix for efficient CSC enrichment and direct in-situ electrochemical monitoring. Flow cytometric analysis demonstrated that the Fmoc-FF hydrogel robustly induced CSC-like phenotypes across breast, cervical, and lung tumor cells (TCs) under mild stiffness conditions (∼10 kPa), significantly lower than the stiffness used in most previously reported matrices. Notably, TCs 3D cultured in the nanofibrous hydrogel led to a two-order-of-magnitude proliferation increase within 5 days. This is attributed to the in situ self-assembly of Fmoc-FF monomers in the presence of cells, generating a dense nanofiber network that tightly encapsulates cells and enhances cell-matrix interactions, even at low seeding density. Furthermore, electrochemical sensors based on the Fmoc-FF hydrogel allow in situ, non-destructive monitoring of dynamic changes in stemness-associated biomarker aldehyde dehydrogenase 1 during TC reprogramming. This approach avoids cell isolation and preserves critical biological information, providing a powerful tool for stemness evaluation. Overall, this study demonstrates the robust stemness-inducing capability and in situ cell monitoring of the self-assembled peptide hydrogel integrated platform for the first time, presenting a promising strategy to enhance in vitro CSC reprogramming efficiency and yield.

肿瘤干细胞（CSCs）对化疗和放疗具有固有的耐药性，是肿瘤复发和转移的关键驱动因素。传统的体外CSC富集模型依赖于肿瘤分离和球形成，通常耗时且效率低下。同时，CSC的分离和表征也面临着挑战。本研究中，由n-芴基甲氧羰基二苯丙氨酸（Fmoc-FF）组成的自组装肽纳米纤维水凝胶多功能平台可作为高效CSC富集和直接原位电化学监测的功能三维矩阵。流式细胞术分析表明，Fmoc-FF水凝胶在轻度刚度条件下（~ 10 kPa）显著低于大多数先前报道的基质中使用的刚度，可在乳房、宫颈和肺部肿瘤细胞（tc）中强烈诱导scs样表型。值得注意的是，在纳米纤维水凝胶中培养的3D TCs在5天内导致两个数量级的增殖增加。这是由于Fmoc-FF单体在细胞存在下的原位自组装，即使在低播种密度下也能产生致密的纳米纤维网络，紧密包裹细胞并增强细胞-基质相互作用。此外，基于Fmoc-FF水凝胶的电化学传感器允许在TC重编程过程中对茎干相关生物标志物醛脱氢酶1的动态变化进行原位、非破坏性监测。这种方法避免了细胞分离，并保留了关键的生物信息，为干细胞性评估提供了有力的工具。总体而言，本研究首次证明了自组装肽水凝胶集成平台具有强大的干细胞诱导能力和原位细胞监测能力，为提高体外CSC重编程效率和产量提供了一个有希望的策略。

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引用次数: 0

Corrigendum to “Nanoparticle-inhibited neutrophil elastase prevents neutrophil extracellular trap and alleviates rheumatoid arthritis in C57BL/6 mice” [Nano Today 50 (2023) 101880] “纳米颗粒抑制中性粒细胞弹性酶防止C57BL/6小鼠的中性粒细胞胞外陷阱和缓解类风湿关节炎”的更正[Nano Today 50 (2023) 101880]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-18 DOI: 10.1016/j.nantod.2025.102919

Min Liu, Siyi Liu, Lin Liu, Jingya Xiu, Tian Zhang, Dawei Chen, Mingxi Qiao, Haiyang Hu, Jiulong Zhang, Xiuli Zhao

引用次数: 0

Corrigendum to “Redox-driven mechanoregulation of invasive TNBC cells using poly(tannic acid) nanospheres” [Nano Today, 66 (2026), 102907] “使用聚单宁酸纳米球对侵袭性TNBC细胞的氧化还原驱动的机械调节”的勘误表[Nano Today， 66 (2026), 102907]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-18 DOI: 10.1016/j.nantod.2025.102917

Minhee Ku , Suhui Jeong , Nara Yoon , Hwain Myeong , Jinwon Kwon , Jaemoon Yang , Sungbaek Seo

引用次数: 0

Cancer models in nanomedicine research: Rethinking in vitro models for translational nanomedicine 纳米医学研究中的癌症模型：对转化纳米医学体外模型的再思考

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-15 DOI: 10.1016/j.nantod.2025.102911

Lucy Wang , Oluwatomilayo Ejedenawe , Stephanie Lheureux , Danielle Rodin , Christine Allen

The U.S. FDA’s recent move to ease mandatory animal testing requirements has renewed scrutiny of in vitro models used in preclinical drug development. In nanomedicine, platforms such as spheroids, organoids, and organ-on-chip have advanced mechanistic modeling, yet the predictive validity of these systems remains limited by the biological relevance of the cell lines they incorporate. This Perspective critically evaluates the translational implications of using a narrow set of immortalized cancer cell lines in nanomedicine research – many of which lack genetic, phenotypic, or demographic alignment with cancer disease biology. Through a literature review of the 50 most cited studies in gynecologic cancer nanomedicine, we reveal an overreliance on just three cell lines in over 60–80 % of surveyed publications. We further show that most available gynecologic cancer cell lines are of European ancestry, with limited representation of global populations, despite growing evidence of population-specific differences in nanomedicine clinical efficacy and toxicity. These findings underscore a critical bottleneck in the development pipeline: the overuse of preclinical models that lack the biological variability necessary for robust clinical translation. As regulatory frameworks increasingly prioritize in vitro data in preclinical evaluation, the need to widen our cancer cell model repertoire becomes increasingly urgent. We propose actionable strategies to improve model representativeness and foster early stakeholder engagement in preclinical research. By embedding these practices into nanomedicine development, the field can strengthen translational outcomes, potentially reducing late-stage failures while better meeting the needs of the global oncology market.

美国食品和药物管理局最近放宽强制性动物试验要求的举措，重新审视了用于临床前药物开发的体外模型。在纳米医学中，球体、类器官和器官芯片等平台具有先进的机制建模，但这些系统的预测有效性仍然受到它们所结合的细胞系的生物学相关性的限制。本展望批判性地评估了在纳米医学研究中使用一组狭窄的永生化癌细胞系的转化意义-其中许多缺乏与癌症疾病生物学的遗传，表型或人口统计学一致性。通过对50个被引用最多的妇科癌症纳米医学研究的文献回顾，我们发现在超过60 - 80% %的调查出版物中过度依赖三种细胞系。我们进一步表明，尽管越来越多的证据表明纳米药物的临床疗效和毒性存在人群特异性差异，但大多数可用的妇科癌细胞系都是欧洲血统，在全球人群中的代表性有限。这些发现强调了开发管道中的一个关键瓶颈：过度使用缺乏强大临床转化所需的生物学变异性的临床前模型。随着监管框架在临床前评估中越来越优先考虑体外数据，扩大我们的癌细胞模型库的需求变得越来越迫切。我们提出了可操作的策略，以提高模型的代表性和促进早期利益相关者参与临床前研究。通过将这些实践纳入纳米医学开发，该领域可以加强转化结果，潜在地减少后期失败，同时更好地满足全球肿瘤市场的需求。

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引用次数: 0

Layered GaPS4 dielectric for two-dimensional transistors 用于二维晶体管的层状GaPS4介电介质

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-13 DOI: 10.1016/j.nantod.2025.102915

Liqun Niu , Zhiren Chen , Guorui Xiao , Zhaowei Zhang , Yinning Zhou , Yu Zhou , Huamin Li , Shen Lai

Developing van der Waals (vdW) high-k dielectric layers is a key factor in achieving high-performance two-dimensional (2D) semiconductor field effect transistors (FETs). Here, we experimentally reveal that layered GaPS₄ flakes exhibit a high dielectric constant of up to 35 and a high capacitance density (∼2.95 μF/cm²), along with a bandgap larger than 4.15 eV. Band alignment of MoS₂/GaPS₄ heterostructure indicates a unipolar-like barrier between MoS₂ and GaPS₄ for electrons of ∼1.92 eV. We employed GaPS₄ as gate dielectric with an equivalent oxide thickness (EOT) of 1 nm in a MoS₂ FET, and the device shows a low gate leakage current of 10⁻¹³ A, a high on/off ratio of ∼3 × 10⁸, and minimal hysteresis (∼20 mV). Theoretical modeling confirms that weak interactions preserve the MoS₂ channel’s inherent electronic properties. Compared to other layered dielectrics, GaPS₄ in MoS₂ FETs demonstrates superior properties in terms of bandgap, dielectric constant, EOT and on/off ratio. These advantages highlight the potential of GaPS₄ for integration into 2D semiconductor FETs.

开发范德华高k介电层是实现高性能二维（2D）半导体场效应晶体管（fet）的关键因素。在这里，我们通过实验揭示了层状GaPS4薄片具有高达35的高介电常数和高电容密度（~ 2.95 μF/cm²），以及大于4.15 eV的带隙。MoS2/GaPS4异质结构的能带排列表明，MoS2和GaPS4之间的电子为~ 1.92 eV的单极势垒。我们在MoS2 FET中采用等效氧化厚度（EOT）为1 nm的GaPS4作为栅极介电介质，该器件显示出10−13 a的低栅极漏电流，高开/关比为~ 3 × 108，最小迟滞（~ 20 mV）。理论模型证实，弱相互作用保留了MoS2沟道固有的电子特性。与其他层状介质相比，MoS2 fet中的GaPS4在带隙、介电常数、EOT和开/关比方面表现出优越的性能。这些优点突出了GaPS4集成到二维半导体场效应管中的潜力。

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引用次数: 0

Polyelectrolyte nanocomplexes responsive to pathological neuronal discharge realize precise drug delivery for treating acute epilepsy via neurotransmitter homeostasis modulation 多电解质纳米复合物响应病理神经元放电，通过调节神经递质稳态，实现治疗急性癫痫的精确给药

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-11 DOI: 10.1016/j.nantod.2025.102916

Xinrui Zhao , Rong Yang , Yage Sun , Wenguang Liu

Abnormal neuronal discharge due to disordered neurotransmitter homeostasis and harsh inflammation in epileptic focus is prone to cause recurrent seizures. However, current difficulties in drug delivery across blood-brain barrier (BBB) and regulation of complex pathological microenvironment hinder complete control of epilepsy with clinical therapies. Herein, a novel microenvironment-responsive drug-loaded polyelectrolyte nanocomplex (HCT-Fu@VB₆) formed by electrostatic self-assembly between tryptophan-modified hydroxypropyl chitosan (HCT) and fucoidan (Fu) with efficient vitamin B₆ (VB₆) loading, is developed for potent epilepsy treating, innovatively aiming to modulate neurotransmitters balance and attenuate the neuroinflammatory responses. Specifically, HCT confers the nanoparticles with specific binding affinity towards L-type amino acid transporter 1 expressed on brain endothelial cells, thereby significantly contributing to enhanced trans-BBB drug delivery efficiency. The fucoidan-containing polyelectrolyte nanocomplexes serve to provide intrinsic antioxidant property. Notably, the prepared polyelectrolyte nanocomplexes are dissociated in response to the mimic pathological neuronal discharges due to disturbed electrostatic equilibrium, facilitating accelerated VB₆ release for enhanced oxidative stress mitigation and effective neurotransmitter homeostasis modulation, acting as a competitive antagonist of ATP-gated purinergic P2RX7. The developed HCT-Fu@VB₆ nanoparticles demonstrate significant therapeutic efficacy as an electrically responsive trans-BBB drug delivery system, remarkably reducing seizure in epileptic rats while maintaining an excellent safety profile.

由于神经递质稳态紊乱和癫痫病灶严重炎症引起的异常神经元放电容易引起反复发作。然而，目前在血脑屏障（BBB）药物传递和复杂病理微环境调控方面的困难阻碍了临床治疗对癫痫的完全控制。本文通过色氨酸修饰的羟丙基壳聚糖（HCT）和高效负载维生素B6 （VB6）的岩藻糖聚糖（Fu）之间的静电自组装形成一种新型微环境响应型载药多电解质纳米复合物（HCT-Fu@VB6），用于有效治疗癫痫，创新地旨在调节神经递质平衡和减轻神经炎症反应。具体来说，HCT赋予纳米颗粒与脑内皮细胞上表达的l型氨基酸转运蛋白1的特异性结合亲和力，从而显著提高了跨血脑屏障给药效率。含岩藻糖苷的聚电解质纳米复合物具有固有的抗氧化性能。值得注意的是，所制备的多电解质纳米复合物在静电平衡被扰乱的模拟病理神经元放电的反应中解离，促进加速VB6的释放，增强氧化应激缓解和有效的神经递质稳态调节，作为atp门控嘌呤能P2RX7的竞争性拮抗剂。开发的HCT-Fu@VB6纳米颗粒作为一种电反应性的跨血脑屏障药物传递系统显示出显著的治疗效果，显著减少癫痫大鼠的癫痫发作，同时保持良好的安全性。

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引用次数: 0

Corrigendum to “Biodegradable multimodal biomaterials with microenvironmental adaptability and orderly delivery of H2S and bFGF for the treatment of spinal cord injury” [Nano Today 66 (2026) 102890] “具有微环境适应性和有序输送H2S和bFGF的可生物降解多模态生物材料用于脊髓损伤治疗”的勘误表[Nano Today 66 (2026) 102890]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-10-09 DOI: 10.1016/j.nantod.2025.102914

Junqing Huang , Jiamen Shen , Yu Huang , Yanfang Zhao , Yibo Ying , Yanran Bi , Liuxi Chu , Xinwang Ying , Qian Xu , Junpeng Xu , Ping Wu , Jiansong Ji , Zhouguang Wang

引用次数: 0

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