化学免疫疗法
材料科学
阿霉素
共价键
对偶(语法数字)
癌症研究
纳米技术
组合化学
癌症
化学
医学
免疫疗法
内科学
有机化学
化疗
艺术
文学类
作者
Xiaogang Wang,Mingjie Dong,Jinlong Yang,Youcong Gong,Jinkun Huang,Qiqi Yang,Haifeng Dong,Jing Zheng
标识
DOI:10.1002/adfm.202408846
摘要
Abstract Chemoimmunotherapy, which integrates chemotherapeutic drugs with immune modulators, has emerged as a promising approach to enhance the generally lackluster clinical outcomes of immunotherapy. Nevertheless, a significant challenge lies in orchestrating multiple events associated with diverse mechanisms that activate antitumor immune responses. Here, a novel approach utilizing dual‐responsive covalent organic frameworks (COFs) co‐encapsulating doxorubicin (DOX) and programmed cell death ligand‐1 (PD‐L1) siRNA (siPD‐L1), termed RDAP, is presented for synergistic chemoimmunotherapy. In this system, COFs modified with poly‐L‐lysine (PLL) can adsorb DOX within their porous structure and bind siPD‐L1 onto their surface via electrostatic interactions. The resulting RDAP formulation can escape from lysosome via the “proton sponge effect” and undergo rupture upon exposure to azoreductase, leading to the efficient release of DOX and siPD‐L1 into the cytoplasm of 4T1 cells. The RDAP, harboring dual therapeutic agents, can effectively eliminate tumor cells and trigger significant immunogenic cell death (ICD) through DOX. Additionally, it concomitantly suppresses PD‐L1 expression in tumor cells, thereby significantly enhancing the antitumor immune response and resulting in synergistically improved antitumor efficacy. In mouse models, RDAP demonstrated exceptional efficacy in eliminating both primary and distant tumors, along with a pronounced antimetastatic effect against 4T1 murine breast‐to‐lung metastasis.
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