Coassembled Nitric Oxide-Releasing Nanoparticles with Potent Antimicrobial Efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA) Strains

Nitric oxide (NO)-releasing nanoparticles are effective nanomedicines with diverse therapeutic advantages compared with small molecule-based NO donors. Here, we report a new class of furoxan-based NO-releasing nanoparticles using a simple, creative yet facile coassembly approach. This is the first time we demonstrated that the coassembled NO-releasing nanoparticles with poly(ethylene glycol)101-block-poly(propylene glycol)56-block-poly(ethylene glycol)101 (Pluronic F127) had potent antimicrobial efficacies against methicillin-resistant Staphylococcus aureus (MRSA) strains. Nanoparticles obtained from the coassembly of either 4-(1-(3-methylpentan-5-ol)oxyl)(3-phenylsulfonyl) furoxan (compound 1) or 4-methoxy(3-phenylsulfonyl) furoxan (compound 2) with Pluronic F127 exhibit 4-fold improved antimicrobial activities compared to their self-assembled counterparts without Pluronic F127. 5(6)-Carboxylfluorescein (CF) leakage experiments further reveal that both coassembled NO-releasing nanoparticles show stronger interactions with lipid bilayers than those self-assembled alone. Subsequently, their strong plasma membrane-damaging capabilities are confirmed under both high-resolution optical microscopy and scanning electron microscopy characterizations. This coassembly approach could be readily applied to other small molecule-based antimicrobials, providing new solutions and important insights to further antimicrobial recipe design.