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One-pot solvothermal synthesis of polyvinyl pyrrolidone and ethylene glycol-modified Cu2SnS3 (PE/CTS) nanomaterials for photothermal immunotherapy 光热免疫治疗用聚乙烯醇吡咯烷酮和乙二醇修饰Cu2SnS3 (PE/CTS)纳米材料的一锅溶剂热合成
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-21 DOI: 10.1016/j.nantod.2025.102876
Huan Ye , Dongxiao Xu , Xiaochuan Zhang , Jing Yan , Yang Zhou , Mingxin Ye , Jianfeng Shen , Lichen Yin , Zhuchao Zhou
Photothermal therapy (PTT) not only ablates tumor tissues, but also activates antitumor immunity by enhancing immunogenicity, which highly relies on photothermal nanoagents (PTNAs) with excellent photothermal effect. Herein, polyvinyl pyrrolidone (PVP) and ethylene glycol (EG)-modified Cu2SnS3 (PE/CTS) nanoparticles (NPs) and nanosheets (NSs) with excellent biocompatibility and stability were synthesized via the one-pot solvothermal method and applied for photothermal immunotherapy. Because of their strong near-infrared (NIR) light absorption and high extinction coefficient, PE/CTS NPs and NSs possessed high photothermal conversion efficiency (PCE) of 39.3 % and 46.8 %, respectively. Furthermore, the superior photothermal effect of PE/CTS NPs over NSs in the NIR-I region was confirmed both in vitro and in vivo, mainly because of the longer blood circulation time, enhanced tumor accumulation, and higher tumor cell uptake level of NPs. As thus, PE/CTS NPs-mediated PTT effectively inhibited growth of 4T1 xenograft tumors in mice. Moreover, it enhanced local/systemic immune responses by inducing the maturation of dendritic cells (DCs) followed by the activation, proliferation, and intratumoral infiltration of T lymphocytes, and it alleviated immunosuppression by promoting the production of M1-phenotype macrophages and the reduction of regulatory T cells (Tregs). Consequently, PE/CTS NPs-mediated PTT notably inhibited the growth of distant tumors. This study highlights the potential of CTS-based nanomaterials for photothermal immunotherapy, broadening the scope of medical applications of ternary metal chalcogenide nanomaterials.
光热疗法(PTT)不仅能消融肿瘤组织,还能通过增强免疫原性来激活抗肿瘤免疫,这在很大程度上依赖于具有优异光热效应的光热纳米剂(PTNAs)。本文采用一锅溶剂热法合成了具有良好生物相容性和稳定性的聚乙烯吡咯烷酮(PVP)和乙二醇(EG)修饰的Cu2SnS3 (PE/CTS)纳米颗粒(NPs)和纳米片(NSs),并将其应用于光热免疫治疗。PE/CTS NPs和NSs具有较强的近红外吸收和较高的消光系数,光热转换效率(PCE)分别为39.3 %和46.8 %。此外,PE/CTS NPs在NIR-I区的光热效应优于NSs,这主要是由于PE/CTS NPs的血液循环时间更长,肿瘤蓄积增强,肿瘤细胞对NPs的摄取水平更高。因此,PE/CTS nps介导的PTT可有效抑制小鼠4T1异种移植肿瘤的生长。此外,它通过诱导树突状细胞(dc)成熟,随后激活、增殖和肿瘤内T淋巴细胞浸润来增强局部/全身免疫反应,并通过促进m1表型巨噬细胞的产生和调节性T细胞(Tregs)的减少来减轻免疫抑制。因此,PE/CTS nps介导的PTT明显抑制远处肿瘤的生长。本研究突出了基于cts的纳米材料在光热免疫治疗中的潜力,拓宽了三元金属硫族纳米材料的医学应用范围。
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引用次数: 0
Corrigendum to “Simultaneous targeting of primary tumor, draining lymph node, and distant metastases through high endothelial venule-targeted delivery” [Nano Today 36 (2021) 101045] “通过高内皮小静脉靶向递送同时靶向原发肿瘤、引流淋巴结和远处转移”的勘误[Nano Today 36 (2021) 101045]
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-20 DOI: 10.1016/j.nantod.2025.102875
Liwei Jiang , Sungwook Jung , Jing Zhao , Vivek Kasinath , Takaharu Ichimura , John Joseph , Paolo Fiorina , Andrew S. Liss , Khalid Shah , Nasim Annabi , Nitin Joshi , Tomoya O. Akama , Jonathan S. Bromberg , Motohiro Kobayashi , Kenji Uchimura , Reza Abdi
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引用次数: 0
Antioxidant glycopolymersomes with dynamic covalent glucose regulation for synergistic pancreatitis-diabetes therapy 具有动态共价葡萄糖调节的抗氧化糖共聚体用于胰腺炎-糖尿病的协同治疗
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-19 DOI: 10.1016/j.nantod.2025.102871
Zhixiong Huang , Jiamin Zhang , Yuyan Qian , Hengxu Liu , Yufen Xiao , Jianzhong Du
Pancreatitis and diabetes mellitus are interconnected pathologies lacking integrated therapeutic strategies. Current insulin-based therapies risk exacerbating pancreatic inflammation, necessitating "drug-free" alternatives. Herein, we report the first dynamic covalent glycopolymersome platform engineered via reversible addition-fragmentation chain-transfer (RAFT) polymerization and macromolecular self-assembly to synergistically address both conditions. The glycopolymersomes, self-assembled from a triblock copolymer poly(ethylene oxide)-block-poly(4-acrylamidophenylboronic acid-stat-N-acryloyl glucosamine)-block-poly(aminoethyl methacrylate) [PEO-b-P(AAPBA-stat-AGA)-b-PAEMA], integrate glucose-responsive phenylboronic acid moieties for sustained blood glucose regulation and conjugated antioxidants (ferulic acid or tyrosine) for reactive oxygen species (ROS) scavenging. In vitro studies demonstrate reversible glucose responsiveness and potent ROS elimination. In vivo, these glycopolymersomes achieve 60 h of normoglycemia in type 1 diabetic mice and accumulate selectively in the pancreas, mitigating oxidative stress, inflammation, and edema in murine models. Overall, this work pioneers the use of dynamic covalent polymer architectures for dual metabolic regulation, offering a blueprint for insulin-free nanomedicine aimed at treating complex metabolic disorders.
胰腺炎和糖尿病是相互关联的病理缺乏综合治疗策略。目前以胰岛素为基础的治疗有加剧胰腺炎症的风险,需要“无药物”替代。在此,我们报告了第一个通过可逆加成-碎片链转移(RAFT)聚合和大分子自组装来协同解决这两种情况的动态共聚物平台。由三嵌段共聚物聚(环氧乙烷)-嵌段聚(4-丙烯酰胺苯基硼酸-stat- n -丙烯酰氨基葡萄糖胺)-嵌段聚(氨基甲基丙烯酸乙酯)[PEO-b-P(AAPBA-stat-AGA)-b-PAEMA]自组装而成的糖共聚体整合了葡萄糖反应性苯硼酸部分,用于持续的血糖调节,结合了抗氧化剂(阿维酸或酪氨酸),用于清除活性氧(ROS)。体外研究证明了可逆的葡萄糖反应性和有效的ROS消除。在体内,这些糖共聚体在1型糖尿病小鼠中达到60 h的正常血糖水平,并在胰腺中选择性积累,减轻小鼠模型中的氧化应激、炎症和水肿。总的来说,这项工作开创了动态共价聚合物结构用于双重代谢调节的先驱,为治疗复杂代谢紊乱的无胰岛素纳米药物提供了蓝图。
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引用次数: 0
The bifunctional nanomaterials of iron-chelating and antioxidant targeting the blood-brain barrier in the injured area alleviated cerebral ischemia-reperfusion injury 铁螯合和抗氧化双功能纳米材料靶向损伤区血脑屏障可减轻脑缺血再灌注损伤
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-19 DOI: 10.1016/j.nantod.2025.102874
Siyu Tian , Qiaoya Zhao , Zhengxun Liu , Mudi Feng , Peina Wang , Yingying Guo , Linhao You , Yan-Zhong Chang
Stroke is a major cause of morbidity and mortality in both developing and developed countries. After thrombolysis, oxidative stress and free iron levels in the area of brain injury rapidly increase, resulting in neural cell death via apoptosis and ferroptosis. Moreover, due to the limitations of the blood-brain barrier, most drugs cannot efficiently reach the injured area to treat the neurons in proximity to the injury. Here we describe nanoliposomes based on the damaged endothelial cell-targeting properties of platelets and the ability of rabies virus peptides to mediate penetration of the blood-brain barrier, carrying the natural antioxidant, lycopene, and the iron chelator, deferoxamine. After treatment with the nanomaterial, the brain injury area of ischemia-reperfusion mice was significantly reduced, and the apoptosis and ferroptosis of brain cells were remarkably improved. This dual-function, targeted nanoparticle represents a new approach for the treatment of stroke and other conditions related to neurological or peripheral ischemia-reperfusion injury.
中风是发展中国家和发达国家发病率和死亡率的主要原因。溶栓后,脑损伤区氧化应激和游离铁水平迅速升高,导致神经细胞凋亡和铁凋亡。此外,由于血脑屏障的限制,大多数药物不能有效地到达损伤区域,对损伤附近的神经元进行治疗。在这里,我们描述了基于血小板受损内皮细胞靶向特性和狂犬病毒肽介导血脑屏障渗透能力的纳米脂质体,它们携带天然抗氧化剂番茄红素和铁螯合剂去铁胺。经纳米材料处理后,缺血再灌注小鼠脑损伤面积明显减少,脑细胞凋亡和铁下垂明显改善。这种具有双重功能的靶向纳米颗粒代表了治疗中风和其他与神经或外周缺血再灌注损伤相关的疾病的新方法。
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引用次数: 0
Corrigendum to “Antigen-capturing oncolytic adenoviruses along with IDO blockade for improved tumor immunotherapy” [Nano Today (2023) 51 101922] “抗原捕获溶瘤腺病毒和IDO阻断剂用于改善肿瘤免疫治疗”的勘误表[纳米今日(2023)51 101922]
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-19 DOI: 10.1016/j.nantod.2025.102872
Chen Xu , Keman Cheng , Xinwei Wang , Jingjing Liu , Jie Liang , Guangna Liu , Yichao Lu , Ming Tang , Dingfei Qian , Liting Chen , Zhenguo Cheng , Zhenning Wang , Xiao Zhao , Funan Liu
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引用次数: 0
Engineering immunomodulatory hydrogels for diabetic wound microenvironment reprogramming 用于糖尿病伤口微环境重编程的工程免疫调节水凝胶
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-18 DOI: 10.1016/j.nantod.2025.102870
Shunfeng Wang , Xinxin Sun , Yi Li , Zhixiao Zhang , Jin Sun , Zhonggui He , Cong Luo , Shenwu Zhang
Diabetic wounds, characterized by impaired healing due to chronic inflammation and immune dysregulation, pose a significant clinical challenge. Traditional therapies often fail to address the complex immunological dysfunction underlying these wounds. Immunomodulatory hydrogels have become a promising therapeutic strategy for promoting macrophage polarization, inhibiting the formation of NETs, and effectively recruiting T cell. This review provides a comprehensive overview of recent advancements in immunoregulatory hydrogels for diabetic wound healing, focusing on their mechanisms of action, design principles, and clinical potential. Additionally, we explore the design principles of immunoregulatory hydrogels, including biomaterial selection, crosslinking strategies, and active drug integration. Finally, we point out the challenges faced by the transformation of immunoregulatory hydrogels into clinical products, and propose future research directions to promote its clinical application.
糖尿病伤口,其特点是愈合受损,由于慢性炎症和免疫失调,提出了重大的临床挑战。传统的治疗方法往往不能解决这些伤口背后复杂的免疫功能障碍。免疫调节水凝胶已成为促进巨噬细胞极化、抑制NETs形成和有效募集T细胞的一种有前景的治疗策略。本文综述了近年来用于糖尿病伤口愈合的免疫调节水凝胶的研究进展,重点介绍了其作用机制、设计原理和临床潜力。此外,我们还探讨了免疫调节水凝胶的设计原则,包括生物材料选择、交联策略和活性药物整合。最后,我们指出了免疫调节水凝胶转化为临床产品所面临的挑战,并提出了未来的研究方向,以促进其临床应用。
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引用次数: 0
Ultralow-cost personal PCRstrip with volumetric heating based on broadband absorption plasmonic fabric for POCT of pathogens 用于病原体POCT的基于宽带吸收等离子体织物的体积加热的超低成本个人pcrat条带
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-15 DOI: 10.1016/j.nantod.2025.102868
Yu Lu , Chang Liu , Qifan Zhou , Yan Huang , Jingwei Yi , Wei Jin , Zhonghua Liu , Bangshun He , Xiangwei Zhao
The diagnosis of respiratory viral infection via reverse transcription-polymerase chain reaction (RT-PCR) is typically conducted in centralized laboratories using bulky equipment, and the procedure requires 1–2 h to complete. To prevent the spread of infectious diseases, there is an urgent need for ultrafast and accessible molecular diagnostic tools for point-of-care testing (POCT). Here, we developed an ultrafast, POC molecular diagnostic PCRstrip capable of detecting influenza A RNA with high sensitivity (1 copy/μL) in just 15 min. Our system integrated reverse transcription, rapid thermocycling and visual detection at ultralow cost. Broadband absorption plasmonic fabric (BAPF) with excellent photothermal effect was fabricated for volumetric photothermal heating excited by a cost-effective white LED. After photothermal PCR, amplification products can be visually detected by a lateral flow paper strip. Clinical validation of 80 nasopharyngeal swab samples collected from patients suspected of influenza A infection demonstrated a clinical sensitivity of 98.4 % and specificity of 100 %. This fast, ultralow-cost and reliable molecular diagnosis strategy is conducive to POCT, offering an effective tool for untrained personnel to detect and control infectious diseases individually.
通过逆转录聚合酶链反应(RT-PCR)诊断呼吸道病毒感染通常在使用笨重设备的集中实验室中进行,该过程需要1-2 h才能完成。为了防止传染病的传播,迫切需要超快速和可获得的分子诊断工具,用于即时检测(POCT)。在这里,我们开发了一种超快速、POC分子诊断pcr条带,能够在15 min内以高灵敏度(1拷贝/μL)检测甲型流感RNA。我们的系统以超低成本集成了逆转录,快速热循环和视觉检测。制备了具有良好光热效应的宽带吸收等离子体织物(BAPF),用于高性价比白光LED激发的体积光热加热。光热PCR后,扩增产物可通过横向流动纸条直观检测。对疑似甲型流感感染患者采集的80份鼻咽拭子样本进行临床验证,临床敏感性为98.4% %,特异性为100% %。这种快速、超低成本、可靠的分子诊断策略有利于POCT,为未经培训的人员单独检测和控制传染病提供了有效的工具。
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引用次数: 0
Bimetallic nanoadjuvant-mediated glutamine metabolism intervention and STING activation for enhanced antitumor immunity 双金属纳米佐剂介导的谷氨酰胺代谢干预和STING激活增强抗肿瘤免疫
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-15 DOI: 10.1016/j.nantod.2025.102866
Jiashi Zhang , Chunzheng Yang , Jia Tan , Bin Liu , Zhuang Yang , Ziyao Li , Jie Ma , Meifang Wang , Binbin Ding , Abdulaziz A. Al Kheraif , Ping’an Ma , Jun Lin
Immune evasion induced by tumor metabolic reprogramming and the low immunogenicity of tumors resulting in insufficient antitumor immune responses have severely hindered the efficacy of immunotherapy. Herein, we design a bimetallic immunoadjuvant with infinite coordination based on Fe and Mn ions as metal connection points, loaded with the glutamine antagonist diazooxonorleucine (DON), to initiate a robust systemic immune response by targeting glutamine metabolism and activating the stimulator of interferon genes (STING) pathway. The nanoadjuvant exhibits stronger capabilities for generating hydroxyl radicals and depleting glutathione, effectively inducing ferroptosis and immunogenic cell death (ICD). Ingeniously, remarkable ferroptosis amplifies oxidative stress and promotes the generation and cytoplasmic leakage of dsDNA, which acts as an immune-enhancing agent synergistically with Mn2+ to trigger the cGAS-STING innate immune pathway. Moreover, this nanoadjuvant can inhibit glutamine metabolism, thereby reversing the immunosuppressive microenvironment and restoring immune cell function while disrupting the redox homeostasis and energy supply of tumor cells, which further sensitizes ferroptosis. Overall, this cascade-enhanced immunotherapy strategy achieves a broader spectrum of immunotherapy by closely combining innate and adaptive immunity via the intervention of glutamine metabolism and ferroptosis. This study facilitates the progress of amino acid metabolism regulation-based cancer therapy and offers a promising treatment strategy for enhancing antitumor immunity.
肿瘤代谢重编程诱导的免疫逃避和肿瘤低免疫原性导致的抗肿瘤免疫应答不足严重阻碍了免疫治疗的效果。在此,我们设计了一种以铁和锰离子为金属连接点的无限配位双金属免疫佐剂,负载谷氨酰胺拮抗剂重氮异诺亮氨酸(DON),通过靶向谷氨酰胺代谢和激活干扰素基因刺激因子(STING)途径来启动强大的全身免疫反应。纳米佐剂具有较强的羟基自由基生成和谷胱甘肽消耗能力,可有效诱导铁凋亡和免疫原性细胞死亡(ICD)。显著的铁凋亡巧妙地放大氧化应激,促进dsDNA的产生和细胞质渗漏,dsDNA作为免疫增强剂与Mn2+协同触发cGAS-STING先天免疫途径。此外,该纳米佐剂可以抑制谷氨酰胺代谢,从而逆转免疫抑制微环境,恢复免疫细胞功能,同时破坏肿瘤细胞的氧化还原稳态和能量供应,进一步致敏铁凋亡。总的来说,这种级联增强的免疫治疗策略通过谷氨酰胺代谢和铁凋亡的干预,将先天免疫和适应性免疫紧密结合,实现了更广泛的免疫治疗。本研究促进了基于氨基酸代谢调节的癌症治疗的进展,为增强抗肿瘤免疫提供了一种有前景的治疗策略。
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引用次数: 0
Disassembly-driven turn-on fluorescent nanoprobe with adaptive signal amplification for quantitative carbonic anhydrase detection in whole blood and enhanced cancer imaging 具有自适应信号放大的可拆卸驱动的荧光纳米探针用于全血中碳酸酐酶的定量检测和增强癌症成像
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-14 DOI: 10.1016/j.nantod.2025.102869
Tenglong Zou , Ye Chen , Suanquan He , Huiling Huang , Zhiyang Yuwen , Dailiang Zhang , Lemeng Zhang , Hongwen Liu
Carbonic anhydrases (CAs), particularly CA Ⅸ, are critical biomarkers in cancer diagnosis and therapy, but quantitative detection in whole blood remains challenging due to intrinsic background fluorescence, limited signal amplification, and interference from blood autofluorescence. Here, we introduce a disassembly-driven fluorescent nanoprobe (SQ-H-SA) leveraging self-assembly, recognition-driven activation, and adaptive signal amplification. SQ-H-SA harnesses squaraine (SQ) dyes that self-assemble into stable, fluorescence-quenched aggregates in aqueous solution; upon CAs binding, the nanoprobe disassembles, enabling SQ monomers to become conformationally shielded within the protein’s hydrophobic pocket, achieving a rapid 45-fold fluorescence enhancement within minutes of interaction with 3 μM CA Ⅸ. SQ-H-SA nanoprobe exhibits good selectivity (with limited interference from serum albumin), sub-nanomolar sensitivity, and large signal-to-background ratio, enabled by ultralow intrinsic fluorescence and protein-assisted amplification. By effectively suppressing blood autofluorescence based on the inner filter effect, SQ-H-SA achieves reliable quantification of endogenous CAs. Notably, SQ-H-SA not only detected elevated CAs levels in untreated lung cancer patients and notable posttreatment reductions consistent with ELISA findings, but also facilitated high-throughput analysis of clinical specimens to improve diagnostic precision in liquid biopsies. Moreover, SQ-H-SA achieves the first selective, cell membrane-specific fluorescence imaging of CA Ⅸ in cancer cells and clinical lung cancer tissues.
碳酸酐酶(CA),特别是CAⅨ,是癌症诊断和治疗中的关键生物标志物,但由于其固有的背景荧光、有限的信号放大和血液自身荧光的干扰,在全血中进行定量检测仍然具有挑战性。在这里,我们介绍了一种分解驱动的荧光纳米探针(SQ-H-SA),利用自组装、识别驱动激活和自适应信号放大。SQ- h - sa利用squaraine (SQ)染料在水溶液中自组装成稳定的荧光猝灭聚集体;在CAs结合后,纳米探针分解,使SQ单体在蛋白质的疏水口袋内成为构象屏蔽,在与3 μ CAⅨ相互作用的几分钟内实现了45倍的荧光增强。SQ-H-SA纳米探针具有良好的选择性(受血清白蛋白的干扰有限),亚纳摩尔灵敏度和大的信本比,通过超低的固有荧光和蛋白质辅助扩增实现。SQ-H-SA基于内部过滤效应有效抑制血液自身荧光,实现内源性CAs的可靠定量。值得注意的是,SQ-H-SA不仅检测到未经治疗的肺癌患者中CAs水平升高,而且与ELISA结果一致,治疗后显著降低,而且有助于临床标本的高通量分析,以提高液体活检的诊断精度。此外,SQ-H-SA在癌细胞和临床肺癌组织中首次实现了CAⅨ的选择性、细胞膜特异性荧光成像。
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引用次数: 0
Aquaporin encoding mRNA mediated water bomb vaccine for cancer immunotherapy 水通道蛋白编码mRNA介导的肿瘤免疫治疗水弹疫苗
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-08-14 DOI: 10.1016/j.nantod.2025.102864
Danhua Zhou , Bin Wang , Jiahui Gao , Ruiying Wu , Yuanji Feng , Kai Hao , Cong Liu , Shasha He , Ruonan Wang , Yanhui Li , Huayu Tian
Inducing immunogenic cell death (ICD) in tumors is a promising strategy for activating systemic antitumor immunity. However, most ICD approaches rely on chemotherapeutic or physical agents that pose challenges in controllability and biosafety. Here, we report a drug-free, mRNA-based strategy that induces a novel form of ICD via a “water bomb” effect. By delivering aquaporin mRNA into tumor cells using nucleic acid nanocarriers, aquaporins are expressed and embedded in the tumor cell membrane. Upon modulation of the transmembrane osmotic gradient, water influx is rapidly amplified through aquaporin channels, leading to extreme cellular swelling, complete membrane rupture, and explosive tumor cell lysis. This unique form of endogenously driven mechanical ICD elicits potent immune activation by concurrently releasing a full spectrum of damage-associated molecular patterns (DAMPs), tumor-specific antigens, and neoantigens in situ, thereby promoting efficient activation of bone marrow-derived dendritic cells (BMDCs) and enhancing subsequent antigen presentation. In a murine melanoma model, this strategy significantly inhibited the growth of both primary and distant tumors, as well as lung metastases. Similarly, in a breast cancer mouse model, it markedly suppressed the growth of subcutaneous tumors. With excellent biocompatibility, tunability, and immune potency, this “water bomb” based approach offers a conceptually new paradigm for cancer immunotherapy via endogenously driven mechanical ICD.
在肿瘤中诱导免疫原性细胞死亡(ICD)是一种很有前途的激活全身抗肿瘤免疫的策略。然而,大多数ICD方法依赖于化疗或物理药物,这在可控性和生物安全性方面构成挑战。在这里,我们报告了一种无药物、基于mrna的策略,通过“水弹”效应诱导一种新型的ICD。利用核酸纳米载体将水通道蛋白mRNA传递到肿瘤细胞中,实现水通道蛋白在肿瘤细胞膜上的表达和包埋。在跨膜渗透梯度的调节下,水通过水通道蛋白通道流入迅速放大,导致细胞极端肿胀,膜完全破裂,肿瘤细胞爆发性溶解。这种独特的内源性驱动机械ICD通过同时释放全谱损伤相关分子模式(DAMPs)、肿瘤特异性抗原和原位新抗原,从而促进骨髓源性树突状细胞(bmdc)的有效激活,并增强随后的抗原呈递,从而引发有效的免疫激活。在小鼠黑色素瘤模型中,该策略显著抑制了原发肿瘤和远处肿瘤以及肺转移瘤的生长。同样,在乳腺癌小鼠模型中,它显著抑制了皮下肿瘤的生长。这种基于“水弹”的方法具有良好的生物相容性、可调性和免疫效力,为通过内源性驱动的机械ICD进行癌症免疫治疗提供了概念上的新范例。
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引用次数: 0
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