An enzyme-responsive and photoactivatable carbon-monoxide releasing molecule for bacterial infection theranostics

J Mater Chem B. 2020 Oct 21;8(40):9325-9334. doi: 10.1039/d0tb01761b.

Abstract

Infections caused by pathogenic bacteria, especially the drug-resistant bacteria, are posing a devastating threat to public health, which underscores the urgent needs for advanced strategies to effectively prevent and treat these intractable issues. Here we report a feasible and effective theranostic platform based on an enzyme-sensitive and photoactivatable carbon monoxide releasing molecule (CORM-Ac) for the successive detection and elimination of bacterial infection. The extracellular bacterial lipase can trigger the excited state intramolecular proton transfer (ESIPT) via elimination of the ester group in CORM-Ac, thus providing a fluorescence switch for an early warning of infection. Subsequently, the potent bactericidal therapy against the model bacterial strains, Staphylococcus aureus (S. aureus) and notorious methicillin-resistant Staphylococcus aureus (MRSA), was readily realized via photoinduced release of CO. In addition, the CORM-Ac and CORM showed good biocompatibility within a wide range of concentrations. The results of an infected animal wound test also demonstrated that the CORM-Ac-loaded gauze was effective in indicating the wound infection and accelerating the wound healing via the photoinduced CO release. The simplicity, functional integration, good biocompatibility and broad adaptability make CORM-Ac very attractive for bacterial theranostic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / radiation effects
  • Bacterial Proteins / metabolism
  • Carbon Monoxide / metabolism*
  • Carboxylic Ester Hydrolases / metabolism
  • Chromones / chemical synthesis
  • Chromones / metabolism
  • Chromones / pharmacology*
  • Chromones / radiation effects
  • Female
  • Fibroblasts / drug effects
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / metabolism
  • Fluorescent Dyes / pharmacology*
  • Fluorescent Dyes / radiation effects
  • Light
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Optical Imaging
  • Precision Medicine / methods
  • Proof of Concept Study
  • Staphylococcal Skin Infections / diagnostic imaging*
  • Staphylococcal Skin Infections / drug therapy*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Chromones
  • Fluorescent Dyes
  • Carbon Monoxide
  • Carboxylic Ester Hydrolases