National Engineering Research Center for Carbohydrate Synthesis/Key Lab of Fluorine and Silicon for Energy Materials and Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022, P. R. China.
College of Life Science, Jiangxi Normal University, Nanchang, 330022, P. R. China.
Nat Commun. 2022 Aug 11;13(1):4712. doi: 10.1038/s41467-022-32453-3.
The prodrug approach has emerged as a promising solution to combat bacterial resistance and enhance treatment efficacy against bacterial infections. Here, we report an adenosine triphosphate (ATP)-activated prodrug system for on-demand treatment of bacterial infection. The prodrug system benefits from the synergistic action of zeolitic imidazolate framework-8 and polyacrylamide hydrogel microsphere, which simultaneously transports indole-3-acetic acid and horseradish peroxidase in a single carrier while preventing the premature activation of indole-3-acetic acid. The ATP-responsive characteristic of zeolitic imidazolate framework-8 allows the prodrug system to be activated by the ATP secreted by bacteria to generate reactive oxygen species (ROS), displaying exceptional broad-spectrum antimicrobial ability. Upon disruption of the bacterial membrane by ROS, the leaked intracellular ATP from dead bacteria can accelerate the activation of the prodrug system to further enhance antibacterial efficiency. In vivo experiments in a mouse model demonstrates the applicability of the prodrug system for wound disinfection with minimal side effects.
前药方法已成为一种有前途的解决方案，可以对抗细菌耐药性并提高治疗细菌感染的疗效。在这里，我们报告了一种三磷酸腺苷（ATP）激活的前药系统，用于按需治疗细菌感染。该前药系统受益于沸石咪唑骨架-8 和聚丙烯酰胺水凝胶微球的协同作用，它们在单个载体中同时输送吲哚-3-乙酸和辣根过氧化物酶，同时防止吲哚-3-乙酸的过早激活。沸石咪唑骨架-8 的 ATP 响应特性允许前药系统被细菌分泌的 ATP 激活，以产生活性氧（ROS），表现出卓越的广谱抗菌能力。当 ROS 破坏细菌膜时，来自死亡细菌的泄漏的细胞内 ATP 可以加速前药系统的激活，从而进一步提高抗菌效率。在小鼠模型中的体内实验证明了该前药系统在伤口消毒方面的适用性，副作用极小。
