Biofilm-Responsive Nano-Antibiotics for Degradation of Extracellular Polymeric Substance Matrix and Reduction of Pathogenicity against Drug-Resistant Bacterial Infections

Methicillin-resistant Staphylococcus aureus (MRSA) poses a major threat to global public health, particularly due to its biofilm-associated refractory infections. The dense three-dimensional structure of the extracellular polymeric substances matrix (EPS) is a key factor contributing to the challenge of eradicating biofilm-associated infections. Therefore, in this study, ultrasmall cobalt selenide nanoparticles (CoSe NPs) were synthesized and modified with dextran (Dex), successfully obtaining dextran-functionalized cobalt selenide nanoparticles (Dex@CoSe NPs). In vitro experimental results showed that Dex@CoSe NPs not only disperse biofilm by degrading components of the extracellular polymeric substance matrix such as amyloid fibers and polysaccharides but also generate reactive oxygen species (ROS) to promote bacterial cell membrane rupture for enhanced bactericidal effects. Additionally, Dex@CoSe NPs reduce MRSA pathogenicity by down-regulating genes related to the quorum sensing system and ABC transporters. More importantly, Dex@CoSe NPs were shown to effectively alleviate both chronic wound infections and systemic infections caused by MRSA. This study thus provides strategic insights for developing ultrasmall nanoparticles specifically designed to combat biofilm-associated infections.