Antibacterial silver core spherical nucleic acids

Abstract

Bacterial drug resistance (DR) has the potential to be one of the most significant medical challenges of the 21st century. Infections involving DR bacterial strains such as methicillin-resistant Staphylococcus aureus (MRSA) or DR Acinetobacter baumannii spread in hospital and community settings and are associated with an increased risk of death. New therapeutic strategies and modalities are needed to treat these DR infections, especially for DR Gram-negative infections. Here, we describe silver-core spherical nucleic acids (Ag-SNAs) as a broad-spectrum antibacterial. Ag-SNAs leverage the broad spectrum antibacterial activity of silver nanoparticles (Ag-NPs), while exhibiting significantly lower (30-fold) minimum inhibitory concentration (MIC) values in comparison to Ag-NPs and reduced toxicity (14-fold) to mammalian cells. Ag-SNAs demonstrate low nanomolar MICs against both DR Gram-negative and DR Gram-positive bacteria in vitro and reduced in vitro toxicity toward human cells vis-à-vis non-derivatized silver nanoparticles. In a topical in vivo wound model involving a multi-DR, clinically-isolated, Gram-negative A. baumannii strain, Ag-SNAs significantly reduced bacterial load as compared to controls (1.51-fold log10 reduction). Our findings open up possibilities for the further development of Ag-SNAs as new antibacterial agents, particularly against challenging DR Gram-negative infections.