Biomimetic Nano-Immunoactivator via Ionic Metabolic Modulation for Strengthened NIR-II Photothermal Immunotherapy.
Biomimetic Nano-Immunoactivator via Ionic Metabolic Modulation for Strengthened NIR-II Photothermal Immunotherapy.
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DOI：
10.1002/smll.202304370
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发表时间：
2023-08
期刊：
影响因子：
13.3
通讯作者：
Xiaodan Wei;Honglin Huang;Junhan Guo;Ningxi Li;Qingzhi Li;Tian Zhao;Geng Yang;Lulu Cai;Hong Yang;Chunhui Wu;Yiyao Liu
中科院分区：
文献类型：
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作者：
Xiaodan Wei;Honglin Huang;Junhan Guo;Ningxi Li;Qingzhi Li;Tian Zhao;Geng Yang;Lulu Cai;Hong Yang;Chunhui Wu;Yiyao Liu
重编程实体瘤的免疫学“冷”环境目前正成为引发强大和全身性抗癌免疫的主流策略。在这里，详细介绍了一种简单且仿生的纳米免疫激活剂（CuS/Z@M4T1），它通过设计具有CuS纳米点（ND）和癌细胞膜的Zn 2+键合的沸石咪唑酯框架-8（ZIF-8）来实现放大近红外II（NIR-II）通过Zn 2+代谢调节进行光热免疫治疗。CuS/Z@M4T1利用CuS NDs的NIR-Ⅱ光热效应和ZIF-8的酸性反应性，迅速引起细胞内Zn 2+池超载，干扰4 T1细胞的代谢通量，从而有效地抑制热休克蛋白的产生，缓解光热疗法（Photothermal Therapy，PTT）的抵抗。因此，如树突状细胞成熟和T细胞浸润所证明的，在体内和体外诱发并启动免疫级联反应。进一步与抗程序性死亡1（aPD-1）组合实现了增强的抗肿瘤功效，其消除了原发性远处肿瘤并强烈抑制肺转移，这是由于增强的光热刺激和aPD-1对细胞毒性T淋巴细胞的增强的协同作用。总的来说，这项工作提供了第一份使用金属有机金属ZIF-8的固有调制特性与aPD-1一起用于增强癌症光免疫治疗的报告，从而激发了一种新的富含离子的纳米材料用于癌症治疗的组合范例。
Reprogramming the immunologically "cold" environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator (CuS/Z@M4T1 ) is detailed by engineering a Zn2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M4T1 rapidly causes intracellular Zn2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.