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

Abstract

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 (S1) to the lowest triplet state (T1). Among these AIE‐PSs, the optimal AIE‐PS (TPA‐DT‐Qy) exhibits the highest generation yield of 1O2 (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.

Molecular engineering to achieve AIE-active photosensitizers with NIR emission and rapid ROS generation efficiency

“…42,43 With their superiority of negligible autofluorescence, low light scattering, deep detection depth, and less light damage to cells, AIE-active PSs with near-infrared (NIR) light are considered to be more favorable for imageguided PDT in comparison with visible light. [44][45][46] Therefore, AIE-active PSs with efficient ROS generation and longwavelength emission are highly and urgently required for effective treatment. 47,48 However, how to obtain a highly efficient and AIE-active PS with rapid and efficient ROS generation used for PDT remains challenging.…”

Synthesis of tetraphenylethene-based D–A conjugated molecules with near-infrared AIE features, and their application in photodynamic therapy

“…In previous works, we and other authors reported some PSs with pyridinium or quinolinium blocks. 51–53 They can accumulate at cellular mitochondria and exhibit excellent mitochondrial targeting. At the same time, pyridinium and quinolinium derivatives also play an electron acceptor role in D–A conjugated molecules.…”

“…57,58 Finally, positively charged pyridinium and quinolinium derivatives were introduced into the receptor parts to target the mitochondria of cancer cells. 51 Accordingly, the main purpose of this work is to develop AIE-PSs with a strong D–A structure to achieve an excellent PDT effect.…”

Molecularly engineered AIEgens with enhanced quantum and singlet-oxygen yield for mitochondria-targeted imaging and photodynamic therapy

“…Signicantly, such AIEactive dyes have exhibited great promise in the eld of biomedicine. [20][21][22][23] Luminogens characteristic of AIE (AIEgens) emit strong uorescence in the aggregated state with high photostability, which is ideal for cell-based and in vivo optical imaging. [24][25][26][27][28][29] In addition, appropriately designed AIEgens, exhibit superior photosensitization of molecular oxygen than common ACQ-based photosensitizers, 8,[30][31][32] thereby offering scope for the development of enhanced FI-guided PDT agents.…”