Imidazole-molecule-capped chitosan-gold nanocomposites with enhanced antimicrobial activity for treating biofilm-related infections

J Colloid Interface Sci. 2018 Dec 1:531:269-281. doi: 10.1016/j.jcis.2018.07.058. Epub 2018 Jul 17.

Abstract

Biofilms that are widely associated with persistent bacterial infections impose a heavy burden on patients primarily due to their formidable resistance to conventional antiseptic drugs and local immune defense. Here, we successfully synthesized functional gold nanocomposites (CS-Au@MMT) by reducing chloroauric acid in the presence of biocompatible chitosan polymers with cationic amine and the small molecule 2-mercapto-1-methylimidazole (MMT). The cationic amine allowed transport of the CS-Au@MMT to the negatively charged sites at the surface of bacterial cells though electrostatic adhesion, with synergistic effects from the gold nanoparticles and MMT then exerting a strong bactericidal effect to inhibit biofilm formation. For established mature biofilms, CS-Au@MMT was able to adhere to the biofilm surface to render nearby bacterial cells inactive, resulting in biofilm rupture. This allowed CS-Au@MMT to penetrate through the biofilm, leading to sustained damage and achieving biofilm elimination. Furthermore, the nanocomposites efficiently inhibited infections induced by mature biofilm in vivo. These findings indicated that the CS-Au@MMT nanocomposites provide ease of synthesis and fabrication, high bactericidal effect, and low toxicity; thus, they show potential as biofilm-disrupting agents for biomedical and industrial applications.

Keywords: Antibacterial activity; Biocompatibility; Gold nanoparticles; N-heterocyclic molecule.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Cell Line
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Escherichia coli / drug effects*
  • Escherichia coli / physiology
  • Escherichia coli Infections / drug therapy
  • Gold / chemistry
  • Gold / pharmacology*
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Mice
  • Nanocomposites / chemistry
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / physiology

Substances

  • 2-mercapto-1-methylimidazole
  • Anti-Bacterial Agents
  • Imidazoles
  • Gold
  • Chitosan