Metal-free radiosensitizers, particularly iodine, have shown promise in enhancing radiotherapy due to their suitable X-ray absorption capacities and negligible biotoxicities. However, conventional iodine compounds have very short circulating half-lives and are not retained in tumors very well, which significantly limits their applications. Covalent organic frameworks (COFs) are highly biocompatible crystalline organic porous materials that are flourishing in nanomedicine but have not been developed for radiosensitization applications. Herein, we report the room-temperature synthesis of an iodide-containing cationic COF by the three-component one-pot reaction. The obtained TDI-COF can be a tumor radiosensitizer for enhanced radiotherapy by radiation-induced DNA double-strand breakage and lipid peroxidation and inhibits colorectal tumor growth by inducing ferroptosis. Our results highlight the excellent potential of metal-free COFs as radiotherapy sensitizers.
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