Photosensitive AIEgens sensitize bacteria to oxidative damage and modulate the inflammatory responses of macrophages to salvage the photodynamic therapy against MRSA

• Published in: Biomaterials Vol. 309; p. 122583
• Main Authors: Wu, Yifan, Li, Jiangao, Zhu, Liwei, Wang, Deliang, Song, Jiayi, Yu, Xiyong, Li, Ying, Tang, Ben Zhong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2024
• Subjects: Aggregation-induced emission; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antimicrobial agents; Bacterial antioxidant metabolism; Humans; Immune responses; Inflammation - drug therapy; Inflammation - pathology; Macrophages - drug effects; Macrophages - metabolism; Methicillin-resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Mice; Oxidative Stress - drug effects; Photochemotherapy - methods; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; RAW 264.7 Cells; Reactive Oxygen Species - metabolism; Staphylococcal Infections - drug therapy; Bacterial antioxidant metabolism; Antimicrobial agents; Aggregation-induced emission; Immune responses; Methicillin-resistant Staphylococcus aureus
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2024.122583

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents. [Display omitted]