Nontoxic Antimicrobial Cationic Peptide Nanoconstructs with Bacteria-Displaceable Polymeric Counteranions

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.