转移
癌症研究
医学
化学免疫疗法
肺
药物输送
免疫疗法
免疫系统
免疫学
癌症
化学
内科学
有机化学
作者
Xiaoxuan Xu,Qiang Wang,Xindi Qian,Yao Wu,Jiaoying Wang,Jie Li,Yaping Li,Zhiwen Zhang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-03-06
卷期号:17 (6): 5354-5372
被引量:10
标识
DOI:10.1021/acsnano.2c08834
摘要
Lung metastasis is a critical cause of cancer mortality and its therapy is largely challenged by the limited drug delivery efficiency and robust immunosuppression in metastatic tumors. Herein, we designed a spatial-drug-laden M1 macrophage system with liposomal R848 inside and fibroblast activation protein protease (FAP)-sensitive phospholipid-DM4 conjugate on the membrane of M1 macrophage (RDM). RDM could preferentially accumulate at the metastatic lesions in lungs and responsively release the therapeutic agents as free drug molecules or drug-loaded nanovesicles. RDM treatment notably enhanced the infiltration of CD3+CD8+ T cells to lung metastasis and, respectively, caused an 8.54-, 12.87- and 2.85-fold improvement of the granzyme-B-, interferon-γ-, and Ki67-positive subtypes versus negative control. Moreover, RDM treatment produced a 90.99% inhibition of lung metastasis in 4T1 models and significant prolongation of survival in three murine lung metastatic models. Therefore, the drug-laden FAP-sensitive M1 macrophage system represents a feasible strategy to target lung metastasis and boost antitumor immunity for antimetastasis therapy.
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