Synergistic photothermal and antibiotic eradication of S. aureus biofilms using targeted, drug-loaded nanoparticle

by Jenkins, Samir; Meeker, Daniel; Miller, Emily; Smeltzer, Mark; Chen, Jingyi

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Resistance to conventional antibiotics is a growing public health concern that is quickly out-pacing the development of new antibiotics. The development of resistance emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. Biofilm formation represents a serious clin. issue that further complicates antimicrobial therapy due to the intrinsic antibiotic resistance it imparts. We used Staphylococcus aureus as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that the loaded constructs can be conjugated to antibodies targeting a species-sp. surface protein as a means of achieving selective directly to the bacterial cell surface. Near-IR laser irradn., at levels within the current safety std. for use in humans, can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable bacteria. The system was initially validated using planktonic bacterial cultures. In the context of an established biofilm, neither photothermal treatment nor antibiotic treatment was sufficient to completely eradicate the biofilm. However, without changing the dosing parameters, the targeted, drug-loaded nanoconstruct was shown to completely eradicate viable bacteria, thus indicating that this synergistic approach could be used to resolve intrinsically-resistant biofilm infections.