Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China.
Department of Biomedical Engineering, College of Engineering, China Pharmaceutical University, Nanjing 210009, China.
ACS Sens. 2022 May 27;7(5):1361-1371. doi: 10.1021/acssensors.1c02485. Epub 2022 Apr 20.
Several photosensitizers have recently been proposed as novel approaches against β-lactamase-producing drug-resistant bacteria. However, these reported photosensitizers are rarely used for accurate recognition of drug-resistant bacteria. To tackle this challenge, the structurally modified photosensitizer CySG-2 based on a lipophilic cationic heptamethine indocyanine near-infrared (NIR) dye (IR-780) and an important synthesis intermediate of cephalosporin antibiotic (GCLE) not only achieved the accurate recognition of TEM-1 methicillin-resistant (MRSA) successfully but also achieved antimicrobial photodynamic therapy (aPDT) in animal models infected by drug-resistant bacteria. Accurate enzyme recognition and efficient photodynamic therapy capabilities allow CySG-2 to achieve one stone with two birds. In addition, CySG-2 could also promote the eradication of internalized MRSA by facilitating the autophagy process, which is synergistic with its capacity of inducing reactive oxygen species generation under NIR laser irradiation for aPDT. Collectively, it is an effective multifunctional photosensitizer with the potential ability to guide the optimal use of different antibiotics and apply them in clinical treatment.
最近有几种光敏剂被提议作为对抗产β-内酰胺酶耐药菌的新方法。然而，这些报道的光敏剂很少用于准确识别耐药菌。为了解决这一挑战，基于疏水性阳离子七甲川吲哚菁近红外（NIR）染料（IR-780）和头孢菌素抗生素（GCLE）重要合成中间体的结构修饰光敏剂 CySG-2 不仅成功地实现了对 TEM-1 耐甲氧西林金黄色葡萄球菌（MRSA）的准确识别，而且在耐药菌感染的动物模型中实现了抗菌光动力治疗（aPDT）。准确的酶识别和高效的光动力治疗能力使 CySG-2 一石二鸟。此外，CySG-2 还可以通过促进自噬过程来促进内化 MRSA 的清除，这与其在 NIR 激光照射下诱导活性氧生成的能力协同作用，用于 aPDT。总的来说，它是一种有效的多功能光敏剂，具有指导不同抗生素最佳使用并将其应用于临床治疗的潜力。
