Nontoxic Antimicrobial Cationic Peptide Nanoconstructs with Bacteria-Displaceable Polymeric Counteranions

Dicky Pranantyo, Cheerlavancha Raju, Zhangyong Si, Xiaofei Xu, Kevin Pethe, En Tang Kang*, Mary B. Chan-Park*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Antimicrobial peptides that target the integrity of bacterial envelopes can eradicate pathogens with little development of resistance, but they often inflict nonselective toxicity toward mammalian cells. The prevailing approach to optimize the selectivity of cationic peptides has been to modify their composition. Instead, we invent a new generation of broad-spectrum antibacterial nanoconstructs with negligible mammalian cell toxicity through a competitive displacement of counter polyanions from the complementary polycations. The nanoconstruct, which has a highly cationic Au nanoparticles (NPs) core shielded by polymeric counterions, is inert in nonbacterial environments. When exposed to negatively charged bacterial envelopes, this construct sheds its polyanions, triggering a cationic Au NP/bacterial membrane interaction that rapidly kills Gram-positive and Gram-negative bacteria. The anionic charge and hydrophilicity of the polyanion provides charge neutralization for the peptide-decorated Au NP core, but it is also bacteria-displaceable. These results provide a foundation for the development of other cationic particles and polymeric counterion combinations with potent antimicrobial activity without toxicity.

Original languageEnglish
Pages (from-to)899-906
Number of pages8
JournalNano Letters
Volume21
Issue number2
DOIs
Publication statusPublished - Jan 27 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
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ASJC Scopus Subject Areas

  • Bioengineering
  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanical Engineering

Keywords

  • anionic polymeric counterion
  • competitive displacement
  • electrostatic nanoconstructs
  • high-density cationic gold nanoparticles
  • no toxicity
  • selective antimicrobials

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