Tailoring nanoparticle-biofilm interactions to increase efficacy of antimicrobial agents against Staphylococcus aureus

Considering the timeline required for the development of novel antimicrobial drugs, increased attention should be given to repurposing existing drugs and improving their antimicrobial efficacy, particularly for chronic infections associated with biofilms. Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are common causes of biofilm-associated infections however each species has a distinct biofilm phenotype resulting in different biofilm matrix characteristics.. Nanoparticles (NPs) have the potential to significantly enhance the delivery of antimicrobial agents into biofilms, however the physicochemical properties which influence these interactions between NPs and the biofilm are not fully understood. The influence of NP surface chemistry on interactions with MRSA and MSSA biofilms was explored in this study. Mesoporous silica nanoparticles (MSNs) with different surface functionalizations (bare-B, amine-D, carboxyl-C, aromatic-A) were synthesised. Following interaction studies, MSNs were loaded with vancomycin (VAN) to observe biofilm eradication. The two negatively charged MSNs (MSN-B and MSN-C) showed a higher VAN loading in comparison to the positively charged MSNs (MSN-D and MSN-A). Cellular binding with MSN suspensions (0.25 mg mL^-1) correlated with reduced viability of both MSSA and MRSA biofilm cells. MSNs were shown to be efficient carriers of vancomycin while also displaying significantly improved efficiency compared to free VAN. This allowed the administration of low MSNs concentrations, while maintaining a high local concentration of the antibiotic surrounding the bacterial cells, indicating a promising novel therapeutic approach for S. aureus biofilm infections.