Imaging and Targeted Antibacterial Therapy Using Chimeric Antimicrobial Peptide Micelles

ACS Appl Mater Interfaces. 2020 Dec 9;12(49):54306-54315. doi: 10.1021/acsami.0c13083. Epub 2020 Nov 25.

Abstract

Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria. Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells. Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications. Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms. In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents. These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.

Keywords: antibacterial therapy; antimicrobial peptide; bacterial targeting; infection; micelles.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Cationic Peptides / therapeutic use*
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Biocompatible Materials / therapeutic use
  • Biofilms / drug effects
  • Disease Models, Animal
  • Drug Design
  • Drug Resistance, Bacterial / drug effects
  • Female
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / physiology
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / physiology
  • Hemolysis / drug effects
  • Lung Diseases / drug therapy
  • Lung Diseases / microbiology
  • Lung Diseases / pathology
  • Mice
  • Mice, Inbred BALB C
  • Micelles*
  • Rats
  • Soft Tissue Injuries / drug therapy*
  • Soft Tissue Injuries / microbiology
  • Soft Tissue Injuries / pathology

Substances

  • Antimicrobial Cationic Peptides
  • Biocompatible Materials
  • Micelles