Mitochondrial-targeted type I/II self-reporting photosensitizer with viscosity-sensitive properties for tumor recognition and apoptosis induction

Abstract

Establishing a dynamic correlation between photodynamic therapy (PDT) processes and changes in mitochondrial viscosity is of significant research value for advancing the development of theranostics technologies for tumors. Nevertheless, research on constructing mitochondrial viscosity-sensitive probes at the single-molecule scale that simultaneously possess high type I/II PDT efficacy for tumors and the ability to visualize therapeutic effects remains lacking. In this work, we developed a novel D-π-A type organic small molecule photosensitizer (TKC), constructed by substituting carbazole with tetraphenylethylene (TPE) as the electron-donating moiety (D) and employing indole iodide salt as the electron-accepting component (A). TKC is capable of performing highly sensitive and specific fluorescence imaging over a wide viscosity range (η, 1.005-1410 cP), enabling real-time in situ imaging of intracellular mitochondrial viscosity as well as accurate differentiation between normal and cancer cells. Furthermore, TKC exhibits efficient type I/II ROS generation capabilities, with a ¹O₂ quantum yield of 3.56, while achieving efficient phototoxicity to tumor cells and inhibition of tumor growth in tumor-bearing mice. More importantly, TKC can monitor the mitochondrial depolarization process and the dynamic changes of mitochondrial viscosity during the process of apoptosis, enabling real-time tracking and self-reporting of treatment effects. Therefore, the fluorescent probe developed in this work, which integrates precise tumor diagnosis, mitochondrial-targeted therapy and dynamic efficacy evaluation, offers an effective strategy for the subsequent advancement of integrated diagnostic and therapeutic fluorescent tools.