Engineering Gram Selectivity of Mixed-Charge Gold Nanoparticles by Tuning the Balance of Surface Charges

Angew Chem Int Ed Engl. 2016 Jul 18;55(30):8610-4. doi: 10.1002/anie.201602965. Epub 2016 Jun 2.

Abstract

Nanoparticles covered with ligand shells comprising both positively and negatively charged ligands exhibit Gram-selective antibacterial action controlled by a single experimental parameter, namely the proportion of [+] and [-] ligands tethered onto these particles. Gram selectivity is attributed to the interplay between polyvalent electrostatic and non-covalent interactions that work in unison to disrupt the bacterial cell wall. The [+/-] nanoparticles are effective in low doses, are non-toxic to mammalian cells, and are tolerated well in mice. These results constitute the first example of rational engineering of Gram selectivity at the (macro)molecular level.

Keywords: Gram specificity; antibiotics; ligands; nanoparticles; surface charge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Drug Tolerance
  • Fatty Acids / chemistry
  • Gold / chemistry*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / isolation & purification
  • Ligands
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Mice
  • Microscopy, Confocal
  • Quaternary Ammonium Compounds / chemistry
  • Static Electricity
  • Sulfhydryl Compounds / chemistry

Substances

  • 11-mercaptoundecanoic acid
  • Fatty Acids
  • Ligands
  • N,N,N-trimethyl(11-mercaptoundecyl)ammonium chloride
  • Quaternary Ammonium Compounds
  • Sulfhydryl Compounds
  • Gold