Mitochondria-Targeted Two-Photon Fluorescent Photosensitizers for Cancer Cell Apoptosis via Spatial Selectability.

Abstract

Organelle-targeted photosensitizers have been reported to be effective cell apoptosis agents. Mitochondria is recognized as an ideal target for cancer treatment due to its central role in oxidative metabolism and apoptosis. Meanwhile, two-photon (TP) fluorescence microscopy has become a powerful tool for fluorescence imaging in biological events based on its minimizing photodamage/photobleaching and intrinsic 3D resolution in deep tissues and in vivo. In this study, a series of novel mitochondrial-targeted TP fluorescent photosensitizers (TP-tracers) are designed, synthesized, and systematically investigated. These TP-tracers exhibit extraordinary anti-interference capability among different cations, anions, and amino acids as well as the insensitivity to the changes of pH and complex biological environments. TP-tracers are further used in fluorescence living cells, Drosophila brains, and zebrafish imaging with low cytotoxicity, excellent mitochondria-targeting, and TP properties. The results demonstrate efficient mitochondria-targeting cell selective apoptosis based on TP-activated cancer cells with highly single cell selectivity, and the pharmacokinetic study reveals that MitoY2 does not have accumulation in rats. It is believed that these molecules hold great potential in TP-related smart phototherapy.