Semiconducting Polymer Nano‐regulators with Cascading Activation for Photodynamic Cancer Immunotherapy.

Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano‐regulator (SPNT) with cascading activation for combinational photodynamic cancer immunotherapy. SPNT comprises an immunoregulator (M‐Trp: 1‐methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker‐cleavable linker. Under near‐infrared photoirradiation, SPNT produces singlet oxygen to induce immunogenic apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M‐Trp for indoleamine 2,3‐dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPNT‐mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis. [ABSTRACT FROM AUTHOR]