Molecular Engineering of Efficient Singlet Oxygen Generators with Near-Infrared AIE Features for Mitochondrial Targeted Photodynamic Therapy

Aggregation-caused fluorescence quenching with insufficient production of reactive oxygen species (ROS) has limited the application of photosensitizers (PSs) in fluorescence-imaging-guided photodynamic therapy (PDT). Aggregation-induced emission PSs (AIE-PSs) exhibit enhanced fluorescence intensity and a high efficiency of ROS generation in the aggregation state, which provides an opportunity to solve the above problems. Herein, a series of AIE-PSs are successfully designed and synthesized by adjusting the D-A intensity through molecular engineering. The photophysical properties and theoretical calculations prove that the synergistic effect of 3,4-ethylenedioxythiophene and quinolinium increases the intramolecular charge transfer effect (ICT) of the whole molecule and promotes the intersystem crossing (ISC) from the lowest excited singlet state (S-1) to the lowest triplet state (T-1). Among these AIE-PSs, the optimal AIE-PS (TPA-DT-Qy) exhibits the highest generation yield of O-1(2) (5.3-fold of Rose Bengal). Further PDT experiments show that the TPA-DT-Qy has a highly efficient photodynamic ablation of breast cancer cells (MCF-7 and MDA-MB-231) under white light irradiation. Moreover, the photodynamic antibacterial study indicates that TPA-DT-Qy has the discrimination and excellent photodynamic inactivation of S. aureus. This work provides a feasible strategy for the molecular engineering of novel AIE-PSs to improve the development of fluorescence-imaging-guided PDT.