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

Abstract 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 (SPN T ) with cascading activation for combinational photodynamic cancer immunotherapy. SPN T 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, SPN T 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. SPN T ‐mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis.