Wang Jia-Li, Xia Feng-Wei, Wang Yun, Shi Hai-Zhu, Wang Li-Juan, Zhao Yu, Song Jia-Xing, Wu Ming-Yu, Feng Shun
Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
ACS Appl Mater Interfaces. 2023 Apr 12;15(14):17433-17443. doi: 10.1021/acsami.2c18835. Epub 2023 Mar 16.
Bacterial infections remain a major cause of morbidity worldwide due to drug resistance of pathogenic bacteria. Photodynamic therapy (PDT) has emerged as a promising approach to overcome this drug resistance. However, existing photosensitizers (PSs) are broad-spectrum antibacterial agents that dysregulate the microflora balance resulting in undesirable side effects. Herein, we synthesized a series of aggregation-induced emission (AIE)-active PSs with a lipophilic cationic AIE core with varying charges, named TBTCP and its derivatives. The association of the difference in their molecular charge with the antibacterial effects was systemically investigated. Among the derivatives presented, TBTCP-SF with the electronegative sulfonate group nulled its ability to bind to and ablate Gram-positive (G+) or Gram-negative (G-) bacteria. TBTCP-QY modified by electropositive quaternary ammonium facilitated binding and augmented the photodynamic antibacterial activity for both G+ and G- bacteria. TBTCP-PEG with hydrophilic neutral ligands selectively bound and inactivated G+ bacteria. Under white-light illumination, TBTCP-PEG ablated 99.9% methicillin-resistant (MRSA) and promoted wound healing in MRSA-infected mice, eliminating MRSA infection both and . Our work provides unprecedented insight into the utility of AIE-active PSs for highly targeted and efficient photodynamic ablation of either G+ or G- bacteria that can be translated to next-generation antibacterial materials.
由于病原菌的耐药性，细菌感染仍然是全球发病的主要原因。光动力疗法（PDT）已成为克服这种耐药性的一种有前途的方法。然而，现有的光敏剂（PSs）是广谱抗菌剂，会破坏微生物群平衡，导致不良副作用。在此，我们合成了一系列具有不同电荷的亲脂性阳离子AIE核的聚集诱导发光（AIE）活性PSs，命名为TBTCP及其衍生物。系统研究了它们分子电荷差异与抗菌效果之间的关系。在所展示的衍生物中，带有带负电磺酸根基团的TBTCP-SF使其与革兰氏阳性（G+）或革兰氏阴性（G-）细菌结合并消融的能力失效。由带正电的季铵修饰的TBTCP-QY促进了结合，并增强了对G+和G-细菌的光动力抗菌活性。带有亲水中性配体的TBTCP-PEG选择性地结合并灭活G+细菌。在白光照射下，TBTCP-PEG消除了99.9%的耐甲氧西林金黄色葡萄球菌（MRSA），并促进了MRSA感染小鼠的伤口愈合，在体内和体外都消除了MRSA感染。我们的工作为AIE活性PSs用于对G+或G-细菌进行高度靶向和高效光动力消融的效用提供了前所未有的见解，这可以转化为下一代抗菌材料。
