Intrinsically Cancer-Mitochondria-Targeted Thermally Activated Delayed Fluorescence Nanoparticles for Two-Photon-Activated Fluorescence Imaging and Photodynamic Therapy

Abstract

A recent breakthrough in the discovery of thermally activated delayed fluorescence (TADF) emitters characterized by small single-triplet energy offsets (ΔE_ST) offers a wealth of new opportunities to exploit high-performance metal-free photosensitizers. In this report, two intrinsically cancer-mitochondria-targeted TADF emitters-based nanoparticles (TADF NPs) have been developed for two-photon-activated photodynamic therapy (PDT) and fluorescence imaging. The as-prepared TADF NPs integrate the merits of (1) high ¹O₂ quantum yield of 52%, (2) sufficient near-infrared light penetration depth due to two-photon activation, and (3) excellent structure-inherent mitochondria-targeting capabilities without extra chemical or physical modifications, inducing remarkable endogenous mitochondria-specific reactive oxygen species production and excellent cancer-cell-killing ability at an ultralow light irradiance. We believe that the development of such intrinsically multifunctional TADF NPs stemming from a single molecule will provide new insights into exploration of novel PDT agents with strong photosensitizing ability for various biomedical applications.

Keywords: cancer-mitochondria-targeted; fluorescence imaging; photodynamic therapy; thermally activated delayed fluorescence (TADF); two-photon activated.