Your browser doesn't support javascript.
loading
Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.
Zhuang, Quan-Quan; Zhang, Zhi-Shan; Zheng, Ting-Jin; Lu, Lin-Yan; Lin, Meng-Ting; Yang, Jia-Lin; Deng, Hao-Hua; Xu, Ying-Ying; Chen, Wei.
Affiliation
  • Zhuang QQ; Department of Pharmacy, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • Zhang ZS; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, 350004, China.
  • Zheng TJ; Department of Laboratory Medicine, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • Lu LY; Department of Laboratory Medicine, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • Lin MT; Department of Pharmacy, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, 362000, China.
  • Yang JL; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, 350004, China.
  • Deng HH; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, 350004, China.
  • Xu YY; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, 350004, China.
  • Chen W; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, 350004, China. DHH8908@163.com.
J Nanobiotechnology ; 22(1): 485, 2024 Aug 13.
Article in En | MEDLINE | ID: mdl-39138462
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.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prodrugs / Disinfection / Reactive Oxygen Species / Copper / Alkaline Phosphatase / Escherichia coli / Anti-Bacterial Agents Limits: Animals Language: En Journal: J Nanobiotechnology Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Prodrugs / Disinfection / Reactive Oxygen Species / Copper / Alkaline Phosphatase / Escherichia coli / Anti-Bacterial Agents Limits: Animals Language: En Journal: J Nanobiotechnology Year: 2024 Document type: Article Affiliation country: Country of publication: