Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria

Hou, Z; Shankar, YV; Liu, Y; Ding, F; Subramanion, JL; Ravikumar, V; Zamudio-Vázquez, R; Keogh, D; Lim, H; Tay, MYF; Bhattacharjya, S; Rice, SA; Shi, J; Duan, H; Liu, XW; Mu, Y; Tan, NS; Tam, KC; Pethe, K; Chan-Park, MB

Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria

Hou, Z Shankar, YV Liu, Y Ding, F Subramanion, JL Ravikumar, V Zamudio-Vázquez, R Keogh, D Lim, H Tay, MYF Bhattacharjya, S Rice, SA

Shi, J Duan, H Liu, XW Mu, Y Tan, NS Tam, KC Pethe, K Chan-Park, MB

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Publication Type:: Journal Article
Citation:: ACS Applied Materials and Interfaces, 2017, 9 (44), pp. 38288 - 38303
Issue Date:: 2017-11-08

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Field	Value	Language
dc.contributor.author	Hou, Z	en_US
dc.contributor.author	Shankar, YV	en_US
dc.contributor.author	Liu, Y	en_US
dc.contributor.author	Ding, F	en_US
dc.contributor.author	Subramanion, JL	en_US
dc.contributor.author	Ravikumar, V	en_US
dc.contributor.author	Zamudio-Vázquez, R	en_US
dc.contributor.author	Keogh, D	en_US
dc.contributor.author	Lim, H	en_US
dc.contributor.author	Tay, MYF	en_US
dc.contributor.author	Bhattacharjya, S	en_US
dc.contributor.author	Rice, SA https://orcid.org/0000-0002-9486-2343	en_US
dc.contributor.author	Shi, J	en_US
dc.contributor.author	Duan, H	en_US
dc.contributor.author	Liu, XW	en_US
dc.contributor.author	Mu, Y	en_US
dc.contributor.author	Tan, NS	en_US
dc.contributor.author	Tam, KC	en_US
dc.contributor.author	Pethe, K	en_US
dc.contributor.author	Chan-Park, MB	en_US
dc.date.issued	2017-11-08	en_US
dc.identifier.citation	ACS Applied Materials and Interfaces, 2017, 9 (44), pp. 38288 - 38303	en_US
dc.identifier.issn	1944-8244	en_US
dc.identifier.uri	http://hdl.handle.net/10453/122474
dc.description.abstract	© 2017 American Chemical Society. Cationic antimicrobial peptides (AMPs) and polymers are active against many multidrug-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 ultralow molecular weight (1450 Da) 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 37 nm 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 a 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 noninflammatory 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.relation.ispartof	ACS Applied Materials and Interfaces	en_US
dc.relation.isbasedon	10.1021/acsami.7b12120	en_US
dc.subject.classification	Nanoscience & Nanotechnology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Polysaccharides	en_US
dc.subject.mesh	Peptides	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Hydrogen Bonding	en_US
dc.subject.mesh	Nanoparticles	en_US
dc.subject.mesh	Methicillin-Resistant Staphylococcus aureus	en_US
dc.title	Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria	en_US
dc.type	Journal Article
utslib.citation.volume	44	en_US
utslib.citation.volume	9	en_US
utslib.for	0904 Chemical Engineering	en_US
utslib.for	0303 Macromolecular and Materials Chemistry	en_US
utslib.for	0306 Physical Chemistry (incl. Structural)	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	09 Engineering	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	44	en_US
pubs.publication-status	Published	en_US
pubs.volume	9	en_US

Abstract:

© 2017 American Chemical Society. Cationic antimicrobial peptides (AMPs) and polymers are active against many multidrug-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 ultralow molecular weight (1450 Da) 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 37 nm 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 a 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 noninflammatory 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/122474