dc.contributor.authorHou, Zheng
dc.contributor.authorShankar, Yogesh Vikhe
dc.contributor.authorLiu, Yang
dc.contributor.authorDing, Feiqing
dc.contributor.authorSubramanion, Jothy Lachumy
dc.contributor.authorRavikumar, Vikashini
dc.contributor.authorZamudio-Vázquez, Rubí
dc.contributor.authorKeogh, Damien
dc.contributor.authorLim, Huiwen
dc.contributor.authorTay, Moon Yue Feng
dc.contributor.authorBhattacharjya, Surajit
dc.contributor.authorRice, Scott A.
dc.contributor.authorShi, Jian
dc.contributor.authorDuan, Hongwei
dc.contributor.authorLiu, Xue-Wei
dc.contributor.authorMu, Yuguang
dc.contributor.authorTan, Nguan Soon
dc.contributor.authorTam, Kam C.
dc.contributor.authorPethe, Kevin
dc.contributor.authorChan-Park, Mary B.
dc.identifier.citationHou, Z., Shankar, Y. V., Liu, Y., Ding, F., Subramanion, J. L., Ravikumar, V., et al. (2017). Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria. ACS Applied Materials & Interfaces, 9(44), 38288-38303.en_US
dc.description.abstractCationic antimicrobial peptides (AMPs) and polymers are active against many multi-drug resistant (MDR) bacteria but only a limited number of these compounds are in clinical use due to their unselective toxicity. The typical strategy for achieving selective antibacterial efficacy with low mammalian cell toxicity is through balancing the ratio of cationicity to hydrophobicity. Herein, we report a cationic nanoparticle self-assembled from chitosan-graft-oligolysine (CSM5-K5) chains with ultra-low molecular weight (1450 Daltons) that selectively kills bacteria. Further, hydrogen bonding rather than the typical hydrophobic interaction causes the polymer chains to be aggregated together in water into small nanoparticles (with about 37nm hydrodynamic radius) to concentrate the cationic charge of the lysine. When complexed with bacterial membrane, these cationic nanoparticles synergistically cluster anionic membrane lipids and produce greater membrane perturbation and antibacterial effect than would be achievable by the same quantity of charge if dispersed in individual copolymer molecules in solution. The small zeta potential (+15 mV) and lack of hydrophobicity of the nanoparticles impedes the insertion of the copolymer into the cell bilayer to improve biocompatibility. In vivo study (using a murine excisional wound model) shows that CSM5-K5 suppresses the growth of methicillin-resistant Staphylococcus aureus (MRSA) bacteria by 4.0 orders of magnitude, an efficacy comparable to that of the last resort MRSA antibiotic vancomycin; it is also non-inflammatory with little/no activation of neutrophils (CD11b and Ly6G immune cells). This study demonstrates a promising new class of cationic polymers -- short cationic peptidopolysaccharides -- that effectively attack MDR bacteria due to the synergistic clustering of, rather than insertion into, bacterial anionic lipids by the concentrated polymers in the resulting hydrogen bonding-stabilized cationic nanoparticles.en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en_US
dc.description.sponsorshipMOH (Min. of Health, S’pore)en_US
dc.format.extent82 p.en_US
dc.relation.ispartofseriesACS Applied Materials & Interfacesen_US
dc.rights© 2017 American Chemical Society (ACS). This is the author created version of a work that has been peer reviewed and accepted for publication by ACS Applied Materials & Interfaces, American Chemical Society (ACS). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1021/acsami.7b12120].en_US
dc.subjectShort Peptidopolysaccharideen_US
dc.titleNanoparticles of short cationic peptidopolysaccharide self-assembled by hydrogen bonding with antibacterial effect against multidrug-resistant bacteriaen_US
dc.typeJournal Article
dc.contributor.researchCentre for Antimicrobial Bioengineeringen_US
dc.contributor.researchNTU Food Technology Centreen_US
dc.contributor.schoolSchool of Chemical and Biomedical Engineeringen_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.description.versionAccepted versionen_US
dc.contributor.organizationSingapore Centre for Environmental Life Sciences Engineeringen_US

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