Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity

ACS Appl Mater Interfaces. 2015 Dec 23;7(50):27602-7. doi: 10.1021/acsami.5b09581. Epub 2015 Dec 8.

Abstract

Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at ≤8 μg/mL. The observed activity may be attributed PCL's responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at ≥2048 μg/mL. suggesting good blood compatibility required for intravenous administration.

Keywords: antimicrobial; drug resistance; nanoparticle; stealth coating; stimulus responsive.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / pathogenicity
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology
  • Ethylene Glycols / chemistry
  • Ethylene Glycols / pharmacokinetics*
  • Humans
  • Lipase / antagonists & inhibitors
  • Lipase / chemistry
  • Nanoparticles / chemistry
  • Polyesters / chemistry
  • Polyesters / pharmacokinetics*
  • Proteolysis / drug effects

Substances

  • Antimicrobial Cationic Peptides
  • Dendrimers
  • Drug Carriers
  • Ethylene Glycols
  • Polyesters
  • poly(epsilon-caprolactone)-b-poly(ethylene glycol)
  • Lipase