Restricting Bond Rotations by Ring Fusion: A Novel Molecular Design Strategy to Improve Photodynamic Antibacterial Efficacy of AIE Photosensitizers

Abstract

In recent years, aggregation-induced emission photosensitizers (AIE-PSs) for antibacterial photodynamic therapy (aPDT) have received increasing attention because of their ability to increase reactive oxygen species (ROS) generation in the aggregation state. However, their antibacterial effect still has great room for improvement. Herein, we propose that if the rotation of some bonds in AIE-PSs is restricted, the nonradiative decay could be further suppressed to boost the generation of fluorescence and ROS, so as to improve their antibacterial efficacy. Following this molecular design strategy, we developed a new class of carbazole group-based AIE-PSs (CPVBA, CPVBP, CPVBP2, and CPVBP3), in which the rotation of phenyl-N bonds is restricted in the carbazole ring. Compared with diphenylamine group-based AIE-PSs with free rotation of phenyl-N bonds, carbazole group-based AIE-PSs showed stronger fluorescence, ROS generation, and antibacterial abilities, demonstrating the feasibility of this new design strategy. Notably, CPVBP3 can enter the entire cell of E. coli to exert its antibacterial effect, and there are few reports of photosensitizers with similar functions. Furthermore, to the best of our knowledge, the light dose (1.2 J/cm2) we used for CPVBP2 to kill Staphylococcus aureus is much lower than that of many reported photosensitizers, indicating great prospects for AIE antimicrobial photosensitizers.

An AIE photosensitizer with unquenched fluorescence based on nitrobenzoic acid for tumor-targeting and image-guided photodynamic therapy

“…In addition, we have recently reported another series of nitrobenzoic acid-based AIE-PSs ( CPVBAs ) with high fluorescence (up to 0.52) and singlet oxygen quantum yields (up to 0.71). 40 These results indicate that AIE-PSs based on nitroaromatic groups can have strong fluorescence and ROS generation abilities. Therefore, it is worthy of attention in image-guided photodynamic therapy.…”

“…39 The spectrum of the white light was published in our previous report. 40 For intracellular ROS detection, approximately 1.0 × 10 5 HeLa cells were seeded into 20 mm dishes, cultured in RPMI 1640 medium overnight at 37 °C under 5% CO 2 . After a 6 h incubation with Biotin-TTVBA (10 μM), the medium was replaced with fresh RPMI 1640 medium containing DCFH-DA (10 μM).…”

In Situ Imaging and Anti-inflammation of 3D Printed Scaffolds enabled by AIEgen

“…Furthermore, AIEgens with aggregation-enhanced reactive oxygen species (ROS) generation have achieved great progress in the field of antibacterial treatment by virtue of photodynamic therapy (PDT). [46][47][48][49][50] Nevertheless, few reports about AIEgens inhibiting bacterial infection and bio-imaging on the 3D scaffolds are presented.…”

Aggregation-induced emission photosensitizer-based photodynamic therapy in cancer: from chemical to clinical

“…In the aggregated state, the fluorescence emission of AIE luminogens (AIEgens) is enhanced, as is their ability to generate ROS [ 29 ]. These properties are the reasons why AIEgens are widely used in biomedical fields such as biomolecular labeling, organelle imaging, cell tracking, antibacterial agents and disease diagnosis [ 30 – 46 ], and even make them excellent candidates to be PSs for PDT [ 47 – 50 ]. AIEgens-based PSs were reported by Liu and Tang et al in 2014, which have attracted extensive attention [ 51 ].…”