癌症研究
免疫疗法
光热治疗
肿瘤微环境
药物输送
转移
细胞毒性T细胞
医学
化学
免疫系统
癌症
免疫学
材料科学
体外
肿瘤细胞
纳米技术
内科学
有机化学
生物化学
作者
Yanan Tan,Jian‐Dong Huang,Yong‐Peng Li,Shanshan Li,Min Luo,Jie Luo,Anne W.M. Lee,Li Fu,Fuqiang Hu,Xin‐Yuan Guan
标识
DOI:10.1002/adhm.202101496
摘要
The major obstacles of anti-PD therapy in metastatic tumors are limited drug delivery in primary tumors and metastatic foci, and the lack of tumor-infiltrating lymphocytes (TILs). Here, the authors constructed a novel cellular membrane nanovesicles platform (M/IR NPs) based on homologous targeting and near-infrared (NIR) responsive release strategy to potentiate PD-1/PD-L1 blockade therapy against metastatic tumors. In tumor-bearing mice, biomimetic M/IR NPs targeted both primary tumors and their lung metastases. Upon laser irradiation, M/IR NPs reduced cancer-associated fibroblasts (CAFs) in tumor microenvironment, thus increasing the penetration of TILs. When shed from homologous tumor cell membranes, positively charged nanoparticles (IR NPs) core can capture released tumor-associated antigens, thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. When the photothermal conversion temperature under NIR-laser is higher than 42 °C, M/IR NPs initiated the rupture of cell membranes and the responsive release of PD-1/PD-L1 inhibitor BMS, which significantly attenuated tumor-associated immunosuppression and synergistically induced T cellular immunity to inhibit the tumor growth and metastasis. Overall, biomimetic M/IR NPs can improve the targeting and therapeutic efficacy of anti-PD therapy in primary tumors and metastases, opening up a new avenue for the diagnosis and treatment of metastatic tumors in the future.
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