肿瘤微环境
癌症研究
重编程
嵌合抗原受体
T细胞
免疫系统
细胞疗法
化学
免疫抑制
细胞
医学
免疫学
肿瘤细胞
生物化学
作者
Haimei Li,Xiuxiu Yang,Zichen Wang,Wenyan She,Yi Liu,Liang Huang,Peng Jiang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-06-15
卷期号:17 (12): 11749-11763
被引量:12
标识
DOI:10.1021/acsnano.3c02592
摘要
Chimeric antigen receptor (CAR) T cell therapy holds great promise in the treatment of hematological malignancies but performs poorly in solid tumors due to the tumor immunosuppressive microenvironment. Herein, a multifunctional nanocatalyst (APHA@CM) was prepared by encapsulating horseradish peroxidase (HRP)-loaded Au/polydopamine nanoparticles (Au/PDA NPs) and Ag2S quantum dots with CAR T cell membranes to improve the CAR T cell therapy in solid tumors. The APHA@CM has excellent multimodal imaging capability to precisely guide the scope and time window for nanocatalyst-induced tumor microenvironment regulation and CAR T cell therapy. The oxidase-like activity of Au NPs inhibited the glycolytic metabolism of tumor cells, reducing lactate efflux, reprogramming tumor immunosuppression, and ultimately increasing CAR T cell activation within the tumors. Additionally, the hypoxia environment of tumors could be relieved by HRP to enhance the Au/PDA NPs-induced synergistic sonodynamic/photothermal therapy (SDT/PTT), thereby promoting the immunogenic cell death of NALM 6 cells and enhancing CAR T cell-mediated immune microenvironment reprogramming. When this strategy was utilized to treat NALM 6 solid tumors, it not only completely eliminated tumors but also formed a long-term immune memory effect to inhibit tumor metastasis and recurrence. This work offers a strategy for CAR T cell therapy in solid tumor.
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