Cationic Telluroviologen Derivatives As Type‐i Photosensitizers for Tumor Photodynamic Theranostics

The hypoxia of the tumor microenvironment (TME) seriously restricts the photodynamic therapy (PDT) effect of conventional type‐II photosensitizers, which are highly dependent on O2. In this work, a new type‐I photosensitizer (TPE‐TeV‐PPh3) consisting of a tetraphenylethylene group (TPE) as a bioimaging moiety, triphenyl‐phosphine (PPh3) as a mitochondria‐targeting group, and telluroviologen (TeV2+) as a reactive oxygen species (O2•−, •OH) generating moiety is developed. The luminescence intensity of TPE‐TeV‐PPh3 increased significantly after specific oxidation by excess H2O2 in the TME without responding to normal tissues via the formation of Te═O bond, which can be used for monitoring abnormal H2O2, positioning, and imaging of tumors. TPE‐TeV‐PPh3 with highly reactive radicals generation and stronger hypoxia tolerance realizes efficient cancer cell killing under hypoxic conditions, achieving 88% tumor growth inhibition. Therefore, TPE‐TeV‐PPh3 with low phototoxicity in normal tissue achieves tumor imaging and effective PDT toward solid tumors in response to high concentrations of H2O2 in the TME, which provides a new strategy for the development of type‐I photosensitizers.