Nano Today最新文献_第6页

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

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 : 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

Cyclic D/L-peptides based nanoparticles regulates dendritic cell maturation and enhances anti-tumor immune response 基于环D/ l肽的纳米颗粒调节树突状细胞成熟并增强抗肿瘤免疫反应

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-18 DOI: 10.1016/j.nantod.2025.102931

Wei Hu , Jiaxi Xu , Mingchen Lv , Min Sun , Zhen Fan , Jianzhong Du

Immunotherapy offers enduring cancer treatment by activating the immune system to eliminate cancer cells, but faces challenges like tumor immune evasion and low immunogenicity. Chirality, crucial in biological interactions, remains underexplored for immune modulation. Inspired by the metal-binding domain of manganese superoxide dismutase, we develop a cyclic D/L peptide for chirality-driven immune activation. The cyclic L-Tyr-D-His-L-Asp-D-His (YhDh) peptide coordinates with Mn²⁺ to self-assemble into nanoparticles, cloak with tumor cell membranes for homologous targeting. Compared to all-L or all-D peptides, YhDh nanoparticles promote costimulatory molecule expression on dendritic cells (DCs). Upon intravenous administration, they are oxidized at melanoma sites with tyrosinase overexpression, enabling photothermal-induced immunogenic cell death (ICD). Chiral peptides synergize with Mn²⁺-mediated cGAS-STING activation and ICD, enhancing DC maturation and T cell infiltration (4.36- and 2.88-fold), suppressing tumor metastasis while establishing immune memory. Such chiral cyclic peptides offer a novel strategy for immune activation by regulating peptide chirality.

免疫疗法通过激活免疫系统来消除癌细胞，提供了持久的癌症治疗，但面临着肿瘤免疫逃避和低免疫原性等挑战。手性在生物相互作用中至关重要，但在免疫调节方面仍未得到充分的研究。受锰超氧化物歧化酶金属结合结构域的启发，我们开发了一种手性驱动免疫激活的环D/L肽。环状的L-Tyr-D-His-L-Asp-D-His （YhDh）肽与Mn2+配合，自组装成纳米颗粒，包裹在肿瘤细胞膜上进行同源靶向。与全l或全d肽相比，YhDh纳米颗粒促进树突状细胞（dc）上的共刺激分子表达。经静脉注射后，它们在酪氨酸酶过度表达的黑色素瘤部位被氧化，使光热诱导的免疫原性细胞死亡（ICD）成为可能。手性肽与Mn2+介导的cGAS-STING激活和ICD协同作用，促进DC成熟和T细胞浸润（分别为4.36和2.88倍），抑制肿瘤转移，同时建立免疫记忆。这种手性环肽通过调节肽的手性为免疫激活提供了一种新的策略。

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引用次数: 0

In situ TEM study of radiation tolerance of Fe-substituted hollandite 铁取代荷兰石耐辐射的原位透射电镜研究

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-17 DOI: 10.1016/j.nantod.2025.102929

Yuhan Li , Tao Ma , Nanjun Chen , Mingyang Zhao , Kyle S. Brinkman , Jake Amoroso , Shenyang Hu , Kai Sun , Li Jiang , Fei Gao , Lumin Wang

Nuclear waste forms are materials designed to encase and isolate radioactive isotopes. This material form ensures safe containment and minimizes the release of harmful radiation into the environment. The radiation stability of the material during radioactive decay of the encapsulated isotopes is an important property to evaluate for waste forms as a long-term storage solution for nuclear waste. In this study, the radiation tolerance of a series of Ba_1.33₋_xCs_xFe_2.66₋_xTi_5.34+xO₁₆ hollandite (x = 0, 0.67, and 1.33), designed as a nuclear waste form, especially for Cs, are investigated under electron and ion beam irradiation with in situ transmission electron microscopy (TEM) characterization at nano and atomic scale. The results show a high resistance to amorphization and inconspicuous Cs loss under ionizing radiation with electron fluences up to 1.26 × 10²⁴ cm⁻², equivalent to an ionizing energy deposition of 3.43 × 10¹⁴ Gy, surpassing the total ionizing dosage of ∼10¹¹ Gy resulting from the beta- and gamma-decay of ¹³⁷Cs over 10 half-lives. However, both Ba- and Cs- end members of the hollandite are completely amorphized below a displacement dose of 0.3 displacement per atom (dpa) under 1.2 MeV heavy ions (Kr³⁺) at 200 ℃ as the result of nano scale displacement cascade quenching, indicating that the structure will not be stable if used to encapsulate transuranic elements (TRU). The results also indicate that the Cs-end member of the hollandite required 60 % higher dose than the Ba-end member to become amorphous. Density Functional Theory (DFT) simulations were performed to elucidate and comprehend the experimental results of the ion irradiation experiments. The high tolerance to electron radiation of the hollandite phases with high loading of beta-decay isotopes also makes it a potential candidate material for the key component in beta voltaic nuclear batteries.

核废料形式是用来包裹和隔离放射性同位素的材料。这种材料形式确保安全密封，并尽量减少有害辐射释放到环境中。在封装同位素放射性衰变过程中，材料的辐射稳定性是评估作为核废料长期储存解决方案的废物形式的重要性质。在本研究中，研究了一系列核废料形式Ba1.33−xCsxFe2.66−xTi5.34+xO16荷兰石（x = 0,0.67和1.33），特别是Cs，在电子和离子束照射下的辐射耐受性，并在纳米和原子尺度上进行了原位透射电子显微镜（TEM）表征。结果表明，在电离辐射下，电子影响高达1.26 × 1024 cm−2，具有很高的非晶化抗性和不明显的Cs损失，相当于3.43 × 1014 Gy的电离能沉积，超过了137Cs在10个半衰期内β和γ衰变产生的总电离剂量~ 1011 Gy。然而，在1.2 MeV重离子（Kr3+）作用下，在200℃下，当位移剂量为0.3位移/原子（dpa）时，由于纳米级位移级联淬火，荷兰石的Ba-和Cs-端成员完全非晶化，这表明如果用于包封超铀元素（TRU），结构将不稳定。结果还表明，荷兰石的cs端成员需要比ba端成员高60 %的剂量才能变成无定形。通过密度泛函理论（DFT）模拟来解释和理解离子辐照实验的结果。具有高负载β衰变同位素的荷兰石相对电子辐射的高耐受性也使其成为β伏打核电池关键部件的潜在候选材料。

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引用次数: 0

Engineering nanozymes for theranostics in urological cancer 工程纳米酶在泌尿系统肿瘤治疗中的应用

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-15 DOI: 10.1016/j.nantod.2025.102930

Xiangyu Zhang , Yongnan Jiang , Bin Liu , Xinlu Yu , Bo Jia , Yulong Dong , Xinquan Gu , Jinru Xue , Kelong Fan , Yuhan Zhang

Urological malignancies are highly prevalent and lethal, with recurrence, late diagnosis, and therapeutic resistance compromising patient survival and quality of life. To address these challenges, tumor microenvironment (TME)-responsive strategies—particularly nanozyme-based catalytic systems—have emerged as promising solutions. Cascade catalytic nanozymes can be selectively activated within the TME to generate reactive oxygen species (ROS) through sequential enzyme-mimicking reactions. Moreover, they catalyze the depletion of intracellular antioxidants, amplifying oxidative stress and enhancing redox-driven therapeutic efficacy. These processes induce regulated cell death pathways such as ferroptosis and cuproptosis while reinforcing tumor immunogenicity. In addition, certain metal-based nanozymes act as imaging contrast agents, integrating diagnosis and therapy within a single platform. The diagnostic potential extends beyond traditional imaging and tissue assays, with urine emerging as a valuable, non-invasive biofluid for complementary analysis. This review summarizes recent progress in nanozyme-based catalytic nanomedicine for urological cancers, focusing on cascade catalytic mechanisms, material design, and multifunctional theranostic applications. Finally, the challenges and future directions of intelligent, urine-compatible, imaging-assisted, and clinically translatable nanozyme systems are discussed toward precision urologic oncology.

泌尿系统恶性肿瘤是非常普遍和致命的，复发、晚期诊断和治疗耐药性影响患者的生存和生活质量。为了应对这些挑战，肿瘤微环境（TME）反应策略，特别是基于纳米酶的催化系统，已经成为有希望的解决方案。级联催化纳米酶可以在TME内选择性激活，通过顺序的酶模拟反应产生活性氧（ROS）。此外，它们催化细胞内抗氧化剂的消耗，放大氧化应激，增强氧化还原驱动的治疗效果。这些过程诱导受调控的细胞死亡途径，如铁下垂和铜下垂，同时增强肿瘤的免疫原性。此外，某些金属基纳米酶作为成像造影剂，将诊断和治疗整合在一个单一的平台上。诊断潜力超越了传统的成像和组织分析，尿液作为一种有价值的、非侵入性的生物液体用于补充分析。本文综述了纳米酶催化纳米药物治疗泌尿系统肿瘤的最新进展，重点介绍了级联催化机制、材料设计和多功能治疗应用。最后，讨论了智能、尿兼容、成像辅助和临床可翻译的纳米酶系统在精准泌尿肿瘤方面的挑战和未来方向。

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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 : 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

Ultra large ion substitute resists Jahn-Teller effects towards high-performance Mn-based P2-Na0.67Ni0.33Mn0.67O2 cathode 超大离子替代物抗jann - teller效应制备高性能mn基P2-Na0.67Ni0.33Mn0.67O2阴极

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-10 DOI: 10.1016/j.nantod.2025.102925

Xiang Ding , Caijiang Jiang , Piluan Li , Yong Fan , Zhibin Cheng , Haonan Li , Liangwei Liu , Yi Xiao , Fang Chen , Lili Han

P2-Na_0.67Ni_0.33Mn_0.67O₂ (NNMO) Mn-based cathode has high discharge voltage/capacity and facile manufacture in sodium-ion batteries (SIBs). Meanwhile, it faces fatal irreversible P2→O2 transition at elevated 4 V and grain cracking during cycles. Herein, Ba²⁺ with a super large ionic radius of 135 pm is incorporated into the Ni²⁺ (0.69 Å) and Mn⁴⁺ (0.53 Å) lattice sites to regulate the MnO6 octahedrons in crystallographic structure. This strategy effectively increases the interlayer spacing from 0.5574 nm to 0.5667 nm and suppresses the Jahn-Teller effects of Mn³⁺ via charge compensation as well as P2→O2 phase transition. These gain effects are fundamentally elucidated by a series of in-situ (i.e. in-situ XRD and in-situ DRT) and ex-situ (e.g. XPS spectra, HRTEM images) characterizations. Theoretical calculations further clarify the reduced diffusion energy barrier and enhanced bulk conductivity and differential charge. The optimized Ba-doped NNMO shows extremely advantageous cycling performance in 1 C (118 mA h g⁻¹@91 % @500 cycles), 5 C (90.8 mA h g⁻¹@73.1 %@2000 cycles), and 10 C (80.9 mA h g⁻¹@68.4 %@2000 cycles) current densities. It also has superior rate capability (80.9 mA h g⁻¹@10 C) and negligible voltage decay of 1 ‰ per cycle. The full-cells assembled with hard carbon display competitive cycle performance (107 mA h g⁻¹@87.1 %@0.1 C@500 cycles) and energy density (261 W h kg⁻¹), demonstrating enormously scientific significance and practical value for high-performance SIBs.

P2-Na0.67Ni0.33Mn0.67O2 （NNMO）锰基阴极具有放电电压/容量高、易于在钠离子电池（sib）中制造的优点。同时，在4 V升高条件下，发生了致命的不可逆P2→O2转变和循环过程中的晶粒开裂。其中，离子半径为135 pm的Ba2+被掺入Ni2+（0.69 Å）和Mn4+（0.53 Å）晶格位点，调控MnO6八面体的晶体结构。该策略有效地将层间距从0.5574 nm增加到0.5667 nm，并通过电荷补偿和P2→O2相变抑制了Mn3+的jan - teller效应。这些增益效应通过一系列原位（即原位XRD和原位DRT）和非原位（如XPS光谱，HRTEM图像）表征得到了基本的阐明。理论计算进一步阐明了降低的扩散能垒和增强的体电导率和微分电荷。优化Ba-doped NNMO显示了极其有利的循环性能1 C(118马  h g−1 @91 % @500周期),5 C(90.8马  h g−1 @73.1 % @2000周期),和10 C(80.9马  h g−1 @68.4 % @2000周期)电流密度。它还具有优越的速率能力（80.9 mA h g−1@10 C）和可忽略不计的电压衰减1 ‰每周期。用硬碳组装的全电池显示出具有竞争力的循环性能（107 mA h g−1@87.1 %@0.1 C@500 cycles）和能量密度（261 W h kg−1），对高性能sib具有巨大的科学意义和实用价值。

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引用次数: 0

Nanoparticle-mediated targeted protein degradation (NanoTPD): Principles, rational design and mechanisms of degradation 纳米颗粒介导的靶向蛋白质降解（NanoTPD）：降解原理、合理设计和机制

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-10 DOI: 10.1016/j.nantod.2025.102926

Yunting Zhang , Keran Wang , Yixiang Yang, Tao Gong, Zhirong Zhang, Renhe Liu, Yao Fu

Targeted protein degradation (TPD) strategies, such as proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), offer precise control over the degradation of both cellular and extracellular proteins, presenting significant potential for clinical benefits. Recently, the emergence of nanoparticle-mediated TPD (NanoTPD) has introduced an innovative alternative. NanoTPD utilizes nanoparticles (NPs) that are biocompatible, surface-tunable, and capable of high drug-loading capacity, enabling more efficient targeted delivery and overcoming the limitations of traditional molecular degraders. This review categorizes NanoTPD into two main approaches: (1) NPs serving as delivery vehicles that carry TPD agents, and (2) NPs acting as intrinsic degraders, such as dual or single-ligand NanoTACs. The latter approach is the primary focus of this article. Furthermore, we examine the two main degradation pathways for NanoTACs: the ubiquitin-proteasome system and the lysosomal pathway. Finally, we highlight key challenges, including gaps in understanding the underlying mechanisms, limitations in nanoparticle uptake and intracellular trafficking, and obstacles to clinical translation that must be addressed to realize the full potential of NanoTPD.

靶向蛋白降解（TPD）策略，如蛋白水解靶向嵌合体（PROTACs）和溶酶体靶向嵌合体（LYTACs），可以精确控制细胞和细胞外蛋白的降解，呈现出显著的临床益处。最近，纳米颗粒介导的TPD （NanoTPD）的出现引入了一种创新的替代方案。NanoTPD利用具有生物相容性、表面可调、高载药能力的纳米颗粒（NPs），实现更有效的靶向递送，克服了传统分子降解剂的局限性。本综述将NanoTPD分为两种主要方法：(1)NPs作为携带TPD药物的递送载体；(2)NPs作为内在降解剂，如双配体或单配体nanotac。后一种方法是本文的主要关注点。此外，我们研究了纳米tac的两种主要降解途径：泛素-蛋白酶体系统和溶酶体途径。最后，我们强调了关键的挑战，包括理解潜在机制的差距，纳米颗粒摄取和细胞内运输的限制，以及必须解决的临床转化障碍，以实现NanoTPD的全部潜力。

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引用次数: 0

Size dependent nephrotoxicity of polystyrene microplastics revealed by single-cell transcriptomics profiling 通过单细胞转录组学分析揭示聚苯乙烯微塑料的大小依赖性肾毒性

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-08 DOI: 10.1016/j.nantod.2025.102924

Chen Wang , Tong Yang , Xueling He , Cui Liu , Ang Ma , Chao Chen , Yunmeng Bai , Huiying Li , Peng Gao , Lirun Zhou , Da Chen , Jigang Wang , Huan Tang

Microplastics (MPs) are emerging environmental contaminants with growing concern over their potential nephrotoxicity. However, their size-dependent effects on kidney function remain poorly understood. Here, we employed single-cell RNA sequencing (scRNA-seq) to systematically investigate the renal cellular responses to polystyrene microplastics (PS-MPs) of different sizes (50 nm, 500 nm, and 5 μm). Our results revealed that proximal tubular (PT) cells and renal immune cells are the primary targets of PS-MPs, exhibiting distinct transcriptomic and functional alterations. Medium- and large-sized particles induced stronger inflammatory responses, oxidative stress, ATP depletion, and apoptosis compared to smaller ones. STAT1 was identified as a key regulator mediating size-dependent inflammation in PT cells, and its knockdown significantly attenuated PS-MPs-induced injury. Immune cells profiling further showed particle size-specific activation patterns, with macrophages and cytotoxic T cells displaying pronounced pro-inflammatory and cytotoxic responses. These findings highlight the importance of particle size in dictating microplastic toxicity and underscore the need for size-specific safety evaluations. This study provides novel mechanistic insights into MPs-induced renal injury and identifies STAT1 as a potential therapeutic target.

微塑料（MPs）是一种新兴的环境污染物，其潜在的肾毒性日益受到关注。然而，它们对肾功能的大小依赖性影响仍然知之甚少。在这里，我们采用单细胞RNA测序（scRNA-seq）系统地研究了不同尺寸（50 nm， 500 nm和5 μm）的聚苯乙烯微塑料（PS-MPs）对肾细胞的反应。我们的研究结果表明，近端小管细胞（PT）和肾免疫细胞是PS-MPs的主要靶点，表现出明显的转录组和功能改变。与小颗粒相比，中、大颗粒诱导的炎症反应、氧化应激、ATP消耗和细胞凋亡更强。STAT1被确定为PT细胞中介导大小依赖性炎症的关键调节因子，其敲低可显著减轻ps - mps诱导的损伤。免疫细胞分析进一步显示颗粒大小特异性激活模式，巨噬细胞和细胞毒性T细胞表现出明显的促炎和细胞毒性反应。这些发现强调了颗粒大小在决定微塑料毒性方面的重要性，并强调了对特定尺寸的安全评估的必要性。这项研究为mps诱导的肾损伤提供了新的机制见解，并确定了STAT1作为潜在的治疗靶点。

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引用次数: 0

Engineered protein corona by Bispecific Antibody endows liposome with enhanced tumor targeting ability and mitigated accelerated blood clearance effect 双特异性抗体工程蛋白冠增强了脂质体的肿瘤靶向能力，减轻了加速血液清除效应

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-04 DOI: 10.1016/j.nantod.2025.102923

Xiaoli Wei , Tianhao Ding , Meili Xi , Kristofer J. Thurecht , Christopher B. Howard , Jiwei Cui , Changyou Zhan , Zui Zhang

One of the major challenges in the development of active targeting nanomedicines is the plasma protein corona (PC), which might interfere with or diminish the targeting function. A novel strategy has emerged by precisely regulating the PC through the utilization of endogenous proteins, which is possible to transform the PC into an integral component that enhances targeting ability. However, the individual variability and fluctuating concentrations of endogenous proteins in plasma limit its practical application. In this study, we employed a bispecific antibody (BsAb) integrating mPEG-scFv (a single chain variable fragment to methoxy polyethylene glycol) and HER2-scFv (human epidermal growth factor receptor 2 scFv) to assembly with liposome. By pre-engineering the PC of liposomes, the targeting function to HER2⁺ cells could be preserved during circulation. Notably, the PC formed by BsAb competitively inhibited the binding of endogenous anti-PEG antibodies, thereby reducing subsequent complement activation and alleviating the accelerated blood clearance (ABC) effect. In tumor-bearing mice, BsAb-sLip demonstrated significant accumulation in HER2⁺ human ovarian cancer cells (SKOV3). In the presence of anti-PEG antibodies after liposome stimulation in mice, BsAb significantly mitigated the ABC effect with prolonged liposome circulation. Consistently, in human serum containing pre-existing anti-PEG antibodies, BsAb suppressed liposome-induced complement activation, inhibited macrophage phagocytosis, and maintained the targeting ability toward HER2⁺ tumor cells. These findings indicated that the engineered PC strategy via BsAb represented an effective targeting approach improving the overall in vivo performance of nanomedicines.

血浆蛋白冠（PC）可能会干扰或削弱活性靶向纳米药物的靶向功能，这是开发活性靶向纳米药物面临的主要挑战之一。利用内源性蛋白对PC进行精确调控，有可能将PC转化为增强靶向能力的有机组成部分。然而，血浆中内源性蛋白的个体差异和浓度波动限制了其实际应用。在这项研究中，我们使用了一种双特异性抗体（BsAb），将mPEG-scFv（甲氧基聚乙二醇单链可变片段）和HER2-scFv（人表皮生长因子受体2 scFv）整合到脂质体中。通过预先设计脂质体的PC，可以在循环过程中保留对HER2+细胞的靶向功能。值得注意的是，BsAb形成的PC竞争性地抑制了内源性抗peg抗体的结合，从而减少了随后的补体活化，减轻了加速血液清除（ABC）效应。在荷瘤小鼠中，BsAb-sLip在HER2+人卵巢癌细胞（SKOV3）中有显著的积累。在脂质体刺激后存在抗peg抗体的小鼠中，BsAb显著减轻了ABC效应，延长了脂质体循环。与此一致的是，在含有预先存在的抗peg抗体的人血清中，BsAb抑制脂质体诱导的补体活化，抑制巨噬细胞吞噬，并保持对HER2+肿瘤细胞的靶向能力。这些发现表明，通过BsAb的工程PC策略是一种有效的靶向方法，可以改善纳米药物的整体体内性能。

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