1. Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.
- Author
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Zhuang QQ, Zhang ZS, Zheng TJ, Lu LY, Lin MT, Yang JL, Deng HH, Xu YY, and Chen W
- Subjects
- Animals, Rats, Ascorbic Acid pharmacology, Ascorbic Acid chemistry, Ascorbic Acid analogs & derivatives, Metal Nanoparticles chemistry, Rats, Sprague-Dawley, Male, Copper chemistry, Copper pharmacology, Prodrugs pharmacology, Prodrugs chemistry, Alkaline Phosphatase metabolism, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Escherichia coli drug effects, Reactive Oxygen Species metabolism, Disinfection methods
- Abstract
Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions., (© 2024. The Author(s).)
- Published
- 2024
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