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Photodynamic therapy is an “old” strategy for cancer therapy featuring clinical safety and rapid working, but suitable photosensitizers for colorectal cancer therapy remain lacking. This study synthesized a novel photosensitizer termed Ce6-GFFY based on a self-assembling peptide GFFY and a photo-responsive molecule chlorin e6 (Ce6). Ce6-GFFY forms macroparticles with a diameter of ∼160 nm and possesses a half-life of 10 h, as well as an ideal tumor-targeting ability in mouse models. Ce6-GFFY effectively penetrates cells and generates numerous reactive oxygen species upon 660 nm laser irradiation. The reactive oxygen species promotes the accumulation of cytotoxic T cells and decrease of myeloid-derived suppressor cells in the tumor microenvironment through immunogenic cell death, thus prohibiting the growth of both primary and metastatic tumors after once treatment. This study not only provides a strategy for photosensitizer development but also confirms a promising application of Ce6-GFFY for colorectal cancer therapy.
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