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Acceptor Engineering for Optimized ROS Generation Facilitates Reprogramming Macrophages to M1 Phenotype in Photodynamic Immunotherapy
Author(s) -
Yang Guang,
Ni JenShyang,
Li Yaxi,
Zha Menglei,
Tu Yao,
Li Kai
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202013228
Subject(s) - reprogramming , photodynamic therapy , macrophage polarization , immunotherapy , tumor microenvironment , cancer research , photosensitizer , chemistry , reactive oxygen species , cancer immunotherapy , macrophage , immune system , immunology , biology , in vitro , cell , tumor cells , biochemistry , photochemistry , organic chemistry
Reprogramming tumor‐associated macrophages to an antitumor M1 phenotype by photodynamic therapy is a promising strategy to overcome the immunosuppression of tumor microenvironment for boosted immunotherapy. However, it remains unclear how the reactive oxygen species (ROS) generated from type I and II mechanisms, relate to the macrophage polarization efficacy. Herein, we design and synthesize three donor–acceptor structured photosensitizers with varied ROS‐generating efficiencies. Surprisingly, we discovered that the extracellular ROS generated from type I mechanism are mainly responsible for reprogramming the macrophages from a pro‐tumor type (M2) to an anti‐tumor state (M1). In vivo experiments prove that the photosensitizer can trigger photodynamic immunotherapy for effective suppression of the tumor growth, while the therapeutic outcome is abolished with depleted macrophages. Overall, our strategy highlights the designing guideline of macrophage‐activatable photosensitizers.