A Near-Infrared-II Fluorescent Nanocatalyst for Enhanced CAR T Cell Therapy against Solid Tumor by Immune Reprogramming

作者：Li, Haimei; Yang, Xiuxiu; Wang, Zichen; She, Wenyan; Liu, Yi^*; Huang, Liang^*; Jiang, Peng^*

来源：ACS Nano, 2023.

DOI：10.1021/acsnano.3c02592

• CAR T cell therapy
• solid tumors
• tumor immunosuppressivemicroenvironment
• immune memory
• the second near-infraredfluorescence
• sonodynamic therapy
• photothermaltherapy

Chimeric antigen receptor (CAR) T cell therapy holdsgreat promisein the treatment of hematological malignancies but performs poorlyin solid tumors due to the tumor immunosuppressive microenvironment.Herein, a multifunctional nanocatalyst (APHA@CM) was prepared by encapsulatinghorseradish peroxidase (HRP)-loaded Au/polydopamine nanoparticles(Au/PDA NPs) and Ag2S quantum dots with CAR T cell membranesto improve the CAR T cell therapy in solid tumors. The APHA@CM hasexcellent multimodal imaging capability to precisely guide the scopeand time window for nanocatalyst-induced tumor microenvironment regulationand CAR T cell therapy. The oxidase-like activity of Au NPs inhibitedthe glycolytic metabolism of tumor cells, reducing lactate efflux,reprogramming tumor immunosuppression, and ultimately increasing CART cell activation within the tumors. Additionally, the hypoxia environmentof tumors could be relieved by HRP to enhance the Au/PDA NPs-inducedsynergistic sonodynamic/photothermal therapy (SDT/PTT), thereby promotingthe immunogenic cell death of NALM 6 cells and enhancing CAR T cell-mediatedimmune microenvironment reprogramming. When this strategy was utilizedto treat NALM 6 solid tumors, it not only completely eliminated tumorsbut also formed a long-term immune memory effect to inhibit tumormetastasis and recurrence. This work offers a strategy for CAR T celltherapy in solid tumor.

• 单位
  华中科技大学; y; 武汉大学