Molecular engineering-facilitated AIE-active type-I photosensitizers for photothermal imaging-guided photodynamic therapy†

Abstract

Despite its multiple advantages, the application of fluorescence imaging-guided photodynamic therapy based on type-II photosensitizers is still restricted by the autofluorescence of organisms and the hypoxic microenvironment of tumors. Optical agents with photothermal imaging ability and radical-based type-I reactive oxygen species (ROS) generation capability, which are exempted from the autofluorescence interference and hypoxia limitation, are thus highly desirable. In this study, we propose a molecular engineering strategy based on electron donor (D)–acceptor (A) systems, which promotes the photothermal conversion as well as the generation of type I ROS by manipulating the electron-donating and electron-withdrawing groups to boost the intersystem crossing and enhance nonradiative decay. Among the four designed D–A conjugated molecules, TPACzPy, composed of electron-donating 9-ethyl-N,N-bis(4-methoxyphenyl)-9H-carbazol-2-amine, π-bridging (2Z,2′Z)-2,2′-(1,4-phenylene)bis(but-2-enenitrile), and electron-withdrawing 1-ethylpyridin-1-ium, exhibits the best comprehensive performance. This compound was thus prepared into biocompatible nanoparticles via a nanoprecipitation method with Pluronic F-127 as the encapsulation matrix. The photothermal performance under 660 nm-laser irradiation and the type I photosensitizing properties under white-light irradiation enable the photothermal imaging-guided photodynamic therapy of 4T1 tumors by the TPACzPy nanoparticles, demonstrating the potential of TPACzPy to be applied in cancer diagnosis and inhibition of tumors.