Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, P. R. China.
School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei 230032, P. R. China.
ACS Nano. 2024 Sep 3;18(35):24327-24349. doi: 10.1021/acsnano.4c06565. Epub 2024 Aug 22.
A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the () cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly "capture" in liquid environments, releasing ROS, VAN and Cu on bacterial surfaces to break down the barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.
由于纳米酶具有优越的稳定性和降低的耐药性，在抗菌药物的应用领域取得了一系列进展。然而，催化产生的活性氧物质 (ROS) 由于靶向能力低和催化活性不足，不足以应对复杂伤口环境中的多药耐药菌 (MDROs)。为了解决这个问题，通过一种简单的方法成功构建了具有靶向细菌能力的化学稳定的铜-没食子酸-万古霉素 (CuGA-VAN) 纳米针；这些纳米针表现出 OXD 样和 GSH-px 样双酶活性，以产生 ROS 并诱导细菌铜死亡样死亡，从而消除 MDRO 感染。实验结果表明，GA 的游离羧酸可以与 () 细胞壁骨架中磷壁酸的游离氨反应。因此，CuGA-VAN 纳米针可以在液体环境中迅速“捕获”，在细菌表面释放 ROS、VAN 和 Cu 以破坏 屏障，破坏生物膜。此外，CuGA-VAN 还能有效促进创面修复细胞增殖和血管生成，促进创面愈合，同时确保生物安全性。根据转录组测序，高度内化的 Cu 会导致铜过载毒性；下调与细菌乙醛酸循环、三羧酸循环和氧化呼吸链相关的基因；并诱导细胞质中的脂质过氧化，导致细菌铜死亡样死亡。在这项研究中，巧妙地设计了 CuGA-VAN 以引发靶向、药物释放、ROS 催化抗菌活性和铜死亡样死亡的级联反应。这为多药耐药感染提供了一个创新的思路。
