State Key Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China; Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea.
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea.
Biomaterials. 2022 Jul;286:121580. doi: 10.1016/j.biomaterials.2022.121580. Epub 2022 May 20.
Multidrug-resistant (MDR) gram-positive bacteria are an inevitable source of infection for hospitalized patients and one of the reasons for the increased proportion of severe diseases. Therefore, constructing smart agents for specific and effective combating infections in vivo caused by MDR gram-positive strains is very urgent. Herein, we reported a structure-oriented design strategy (SODS) to reasonably construct an organic photo-antimicrobial near-infrared (NIR) AIEgen BDPTV equipped with a phenylboronic acid moiety, which could be bound to the thick peptidoglycan layer of MDR gram-positive bacteria, resulting in a tight distribution with the cell wall in a confined space. Compared to the contrast compounds DQVTA and DPTVN, upon photoirradiation of AIEgen BDPTV, the generation of abundant and highly toxic reactive oxygen species (ROS) irreversibly destroys MDR gram-positive bacteria through photodynamic therapy, which is better than commercial photosensitizers (including methylene blue, chlorin e6, and protoporphyrin IX) and antibiotic (cefoxitin). As a proof of concept, in vitro experimental results showed that methicillin-resistant Staphylococcus aureus (MRSA) were completely killed using AIEgen BDPTV. More importantly, AIEgen BDPTV was capable of successfully combating MRSA-infected wounds of mice, but not Escherichia coli (E. coli)-infected wounds. We hope that this strategy could provide a new method to design powerful AIEgens to avoid the overuse and misuse of antibiotics.
耐多药（MDR）革兰阳性菌是住院患者感染的必然来源，也是严重疾病比例增加的原因之一。因此，构建针对 MDR 革兰阳性菌引起的体内感染的智能药物来进行特异性和有效治疗非常紧迫。在此，我们报告了一种基于结构的设计策略（SODS），合理构建了一种带有苯硼酸部分的有机光抗菌近红外（NIR）AIE 剂 BDPTV，它可以与 MDR 革兰阳性菌的厚肽聚糖层结合，导致与细胞壁在有限空间内紧密分布。与对照化合物 DQVTA 和 DPTVN 相比，AIE 剂 BDPTV 经光照射后，通过光动力疗法产生大量且毒性高的活性氧（ROS），不可逆地破坏 MDR 革兰阳性菌，其效果优于商业光敏剂（包括亚甲蓝、氯乙酮和原卟啉 IX）和抗生素（头孢西丁）。作为概念验证，体外实验结果表明，AIE 剂 BDPTV 可完全杀死耐甲氧西林金黄色葡萄球菌（MRSA）。更重要的是，AIE 剂 BDPTV 能够成功治疗感染 MRSA 的小鼠伤口，而不能治疗感染大肠杆菌（E. coli）的伤口。我们希望该策略可以为设计强大的 AIE 剂提供新方法，以避免抗生素的过度使用和滥用。
