(760c) Modulating Antimicrobial Activity and Mammalian Cell Biocompatibility with Glycosylated Miktoarm Star Polymers | AIChE

(760c) Modulating Antimicrobial Activity and Mammalian Cell Biocompatibility with Glycosylated Miktoarm Star Polymers


Si, Z. - Presenter, Nanyang Technological University
Wong, E. H. H., The University of New South Wales (UNSW)
Chan-Park, M. B., Nanyang Technological University
The development of novel reagents and antibiotics for combating multi-drug resistance bacteria has been receiving significant attention in recent years. The use of synthetic biomacromolecules/nanoparticles prepared via controlled polymerization techniques is regarded as one of the most promising approaches to overcome such challenge because of the ability to precisely engineer the chemical functionality, and hence the biological properties of the nanomaterial (Lam et al., 2016).Several research groups have reported on the synthesis of antimicrobial polymers to combat the rise of antibiotic-resistant pathogens. However, the majority of these materials exhibit poor selectivity (Hancock and Sahl, 2006). Even though they are effective in killing bacteria, they are inherently harmful towards healthy mammalian cells, which hinder their potential for clinical applications.

In here, we describe the fabrication of new antimicrobial star polymers (< 30 nm in size) consisting of mixtures of polylysine and glycopolymer arms that not only possess good antimicrobial efficacy towards Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) (with MIC values as low as 16 μg mL-1), but are also non-hemolytic (HC50 > 10000 μg mL-1) and exhibit excellent mammalian cell biocompatibility. This new class of antimicrobial star polymers is prepared via a strategic combination of modern synthetic polymer chemistry protocols that entails click chemistry, reversible addition fragmentation chain transfer (RAFT) polymerization, N-carboxyanhydride ring-opening polymerization (NCA-ROP), and macromolecular assembly/cross-linking. The antimicrobial activity and mammalian cell biocompatibility of the star nanoparticles can be tuned efficiently depending on the molar ratio of polylysine to glycopolymers arms and the type of sugars employed (e.g., glucosamine, glucose and galactose). The technology described herein thus represents an innovative and effective approach in fighting deadly infectious diseases.