Time‐Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE‐Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Abstract

Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA‐BQ, by a one‐step reaction. 4TPA‐BQ presents aggregation‐induced emission features. Owing to the aggregation‐induced reactive oxygen species generated and a sufficiently small ΔEST, 4TPA‐BQ shows a satisfactorily high 1O2 generation efficiency of 97.8 %. In vitro and in vivo experiments confirmed that 4TPA‐BQ exhibited potent photodynamic antibacterial performance against ampicillin‐resistant Escherichia coli with good biocompatibility in a short time (15 minutes). When the incubation duration persisted long enough (12 hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time‐dependent fluorescence‐guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA‐BQ reveals new design principles for the implementation of efficient PSs in clinical applications.

Organic Photo-antimicrobials: Principles, Molecule Design, and Applications

“…AIE-active PSs (4TPA-BQ) for highly efficient and selective bacterial elimination. Reprinted with permission from ref . Copyright 2020 John Wiley and Sons.…”

Aggregation-Induced Emission Nanoparticles for Single Near-Infrared Light-Triggered Photodynamic and Photothermal Antibacterial Therapy

“…Another challenge for current PS-based PTT and PDT applications is the limited absorption efficiency of PSs by bacteria and severe aggregation resulting in poor luminescence. Recently, the findings of the AIE phenomenon have provided an alternative to antibacterial therapy. , This is different from traditional fluorogens in that the fluorophores with an AIE effect (AIEgens) can achieve “off–on” fluorescence properties upon aggregate formation because of the prohibition of energy dissipation and restriction of intramolecular motion (RIM). Owing to the RIM mechanism, AIEgens could also generate sufficient ROS in the aggregate state, resulting in AIE-based PSs being more promising for clinical PDT applications. − Although the AIE effect mainly restricts the rotor-like structure from intramolecular motion, some free rotor-like structures can also be used.…”

“…Recently, the findings of the AIE phenomenon have provided an alternative to antibacterial therapy. 22,23 This is different from traditional fluorogens in that the fluorophores with an AIE effect (AIEgens) can achieve "off−on" fluorescence properties upon aggregate formation because of the prohibition of energy dissipation and restriction of intramolecular motion (RIM). Owing to the RIM mechanism, AIEgens could also generate sufficient ROS in the aggregate state, resulting in AIE-based PSs being more promising for clinical PDT applications.…”

A Bacteria‐Responsive Porphyrin for Adaptable Photodynamic/Photothermal Therapy

“…[3][4][5][6][7][8][9][10] Porphyrin-based PTT and PDT are non-contact, convenient, and effective therapeutic methods with low risk in generating drug resistance, and have been applied in clinical treatments for bacterial infections. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] In general, porphyrin derivatives with heavy atoms, cations, and appropriate substituents are commonly used in antimicrobial PDT owing to their high yield of reactive oxygen species, good affinity with bacterial membranes, and non-stacking properties. [29][30][31][32] While for PTT treatments, porphyrin derivatives with changed π electrons, larger conjugated structures, and aggregated morphologies are usually designed because of their red-shifted absorption and high non-radiative decay efficiency.…”