(135i) Block Copolymer Nanoparticles Remove Biofilms of Drug-Resistant Gram-Positive Bacteria By Nanoscale Bacterial Debridement

Antimicrobial resistance has become a global healthcare crisis. Compounded with the evolution of multi-drug resistance, bacteria also develop biofilms to protect themselves, so that biofilm-associated infections are extremely difficult to treat. Antibiotics can be up to x1000 less effective to biofilms as compared with the planktonic form. Once developed into the biofilm form, it will become highly resistant to conventional antibiotics. Many antibiotics, natural antimicrobial peptides and synthetic antimicrobial agents have been studied as anti-biofilm agents but the general efficacy is still not high. Further, they usually suffer from the problem of toxicity and limited life span. Recently, we have developed a novel antibiofilm cationic copolymer nanoparticle that has excellent biofilm removal capability; the nanoparticle is self-assembled from dextran-block-(poly((3-acrylamidopropyl) trimethylammonium chloride(AMPTMA)-co-butyl methacrylate (BMA)) (DA95B5). Interestingly, the polysaccharide-based amphiphilic copolymer DA95B5 self-assembles into nanoparticle form which does not have any antibacterial effect but exhibits excellent preformed biofilm removal ability. As the cationic charge and hydrophobic segments are hidden inside the core of nanoparticles, the latter does not have any bacterial killing ability; however, the antifouling shell of the polysaccharide as well as the nanoparticles form, enhances the biofilm dispersal ability by a mechanism we termed “nanoscale bacterial debridement”. Cryo-TEM and confocal microscopy show that the nanoparticle can penetrate into the biofilm and form a coating around the negatively charged bacteria to weaken the cell-biofilm interaction. Our in vitro results showed that the polymeric nanoparticles exhibit antibiofilm ability towards several multi-drug resistant and clinically relevant Gram-positive bacterial strains, with efficacy much higher and/or similar to the conventional standard antibiotics. Our in vivo data corroborates that such nanoparticles possess MRSA biofilm removal efficacy that is higher than vancomycin. Further, both in vitro and in vivo data showed our nanoparticles have good biocompatibility with low hemolysis and cytotoxicity. Overall, this novel biofilm removal platform of a cationic non-fouling nanoparticle provides exciting opportunities for treatment of multi-drug resistant biofilm infections which may have widespread applications.