Block Copolymer Nanoparticles Remove Biofilms of Drug-Resistant Gram-Positive Bacteria By Nanoscale Bacterial Debridement

Bacterial infection has become the main threat to human, especially the biofilm associated infections. Once developed into biofilm form, it will become more resistant to the conventional antibiotics. Hence, many antibiotics, natural antimicrobial peptides and synthetic antimicrobial agents have been studied as antibiofilm agents. However, they are usually suffered from the problem of toxicity and limited life span. Therefore, a novel antibiofilm cationic copolymer has been synthesized to study both the antibacterial and antibiofilm ability. Interestingly, the polysaccharide-based amphiphilic copolymer can self-assembled into nanoparticle form which don’t have any antibacterial effect but excellent preformed biofilm removal ability. Within the cationic charge and hydrophobic segments hidden inside the core of nanoparticles, the bacterial killing ability became disappeared; however, the antifouling shell of the polysaccharide as well as the nanoparticles form enhanced the biofilm dispersal ability by the mechanism we called “nanoscale bacterial debridement”. Our in vitro results showed that the polymeric nanoparticles have the antibiofilm ability towards several multi-drug resistant and clinically relevant strains, with the efficacy much higher and/or similar to the conventional standard antibiotics. In vivo data also showed that such nanoparticles have MRSA biofilm removal efficacy higher than vancomycin. Further, both the in vitro and in vivo data showed our nanoparticles have good biocompatibility with low hemolysis and cytotoxicity. Overall, this novel biofilm removal approach provides exciting opportunities for treatment of multi-drug resistant biofilm infections and which further may have widespread applications.