内化
肿瘤微环境
TLR7型
药物输送
免疫疗法
癌细胞
癌症免疫疗法
癌症研究
免疫系统
细胞
材料科学
癌症
细胞生物学
纳米技术
化学
Toll样受体
生物
先天免疫系统
免疫学
生物化学
遗传学
作者
Xilin Li,Jingmei Pan,Yan Li,Funeng Xu,Jianwen Hou,Jing Wang,Shaobing Zhou
出处
期刊:ACS Nano
[American Chemical Society]
日期:2022-03-24
卷期号:16 (4): 5778-5794
被引量:23
标识
DOI:10.1021/acsnano.1c10892
摘要
How to precisely reprogram tumor-associated macrophages (TAMs) and combine them with immunogenic cell death (ICD) is still a great challenge in enhancing the antitumor immunotherapeutic effect. Here, we developed a localized drug delivery system with a step-by-step cell internalization ability based on a hierarchical-structured fiber device. The chemotherapeutic agent-loaded nanomicelles are encapsulated in the internal chambers of the fiber, which could first be internalized by actively targeting tumor cells to induce ICD. Next, the rod-like microparticles can be gradually formed from long to short shape through hydrolysis of the fiber matrix in the tumor microenvironment and selectively phagocytosed by TAMs but not to tumor cells when the length becomes less than 3 μm. The toll-like receptors 7 (TLR7) agonist imiquimod could be released from these microparticles in the cytoplasm to reprogram M2-like TAMs. The in vivo results exhibit that this localized system can synergistically induce an antitumor immune response and achieve an excellent antitumor efficiency. Therefore, this system will provide a promising treatment platform for cancer immunotherapy.
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