Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications

New generation antimicrobial agents are expected to exhibit non-metabolic killing mechanisms, high killing potency and biocompatibility. We synthesized a cationic chitosan derivative and an anionic chitosan derivative – specifically an α-poly(L)lysine side-grafted chitosan (CS-PLL) and an anionic ci...

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Main Authors: Pranantyo, Dicky, Kang, En-Tang, Chan-Park, Mary B.
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/154042
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1540422023-02-28T20:00:01Z Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications Pranantyo, Dicky Kang, En-Tang Chan-Park, Mary B. School of Chemical and Biomedical Engineering Lee Kong Chian School of Medicine (LKCMedicine) School of Physical and Mathematical Sciences Centre of Antimicrobial Bioengineering Engineering::Chemical engineering::Polymers and polymer manufacture Bacterial Metabolism Biocompatible Polymer New generation antimicrobial agents are expected to exhibit non-metabolic killing mechanisms, high killing potency and biocompatibility. We synthesized a cationic chitosan derivative and an anionic chitosan derivative – specifically an α-poly(L)lysine side-grafted chitosan (CS-PLL) and an anionic citraconyl anhydride (CA) modified polylysine side graft for chitosan (CS-PLL-CA). The β-carboxylic amide of CS-PLL-CA is pH-labile and self-cleavable under pH 6 or below. When we mixed the cationic (CS-PLL) and anionic (CS-PLL-CA) peptidosaccharide copolymers, they self-assembled, due to electrostatic charge interactions, into nanomicelles (NMs) with the oppositely charged peptides in the core and the chitosan polysaccharide arms on the shell. The NMs exhibited high hemo- and cytocompatibility (nontoxic) at physiological pH of 7.4, due to the chitosan protection on the shell and charge neutralization on the core. Upon reaching the bacterial infection site, the chitosan shell interacted and accumulated around the bacteria. The bacterial infection sites in the body usually show localized acidity as a result of the combined actions of bacterial metabolism and host immune response, and the pH can decrease to as low as 5.5. At this low pH, the β-carboxylic amide bond of the anionic polypeptide gradually hydrolyzed to expose the initial cationic amine moieties, causing the NMs to ‘decompose’ into individual CS-PLL and ‘spill’ the cationic molecules which then disrupted and killed the bacteria. This ‘smart’ bacteria-recognizing chitosan-decorated nanosystem opens the pathway to explore other anionic and cationic and biocompatible polymers for ‘stealth’ delivery of antimicrobial polypeptide, and ‘on-demand’ recovery of the cationic parts to kill bacteria at infection sites. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Published version This work was funded and supported by the Singapore Ministry of Education Tier 3 Grants (MOE2013-T3-1-002 and MOE2018-T3-1-003), ASTAR RIE2020 Advanced Manufacturing and Engineering (AME) IAP-PP Specialty Chemicals Programme Grant (No. A1786a0032), and NTU NAFTEC Funding. 2021-12-15T03:00:59Z 2021-12-15T03:00:59Z 2021 Journal Article Pranantyo, D., Kang, E. & Chan-Park, M. B. (2021). Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications. Biomaterials Science, 9(5), 1469-1890. https://dx.doi.org/10.1039/D0BM01382J 2047-4849 https://hdl.handle.net/10356/154042 10.1039/D0BM01382J 5 9 1469 1890 en MOE2013-T3-1-002 MOE2018-T3-1-003 A1786a0032 Biomaterials Science © 2021 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported License. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Chemical engineering::Polymers and polymer manufacture
Bacterial Metabolism
Biocompatible Polymer
spellingShingle Engineering::Chemical engineering::Polymers and polymer manufacture
Bacterial Metabolism
Biocompatible Polymer
Pranantyo, Dicky
Kang, En-Tang
Chan-Park, Mary B.
Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
description New generation antimicrobial agents are expected to exhibit non-metabolic killing mechanisms, high killing potency and biocompatibility. We synthesized a cationic chitosan derivative and an anionic chitosan derivative – specifically an α-poly(L)lysine side-grafted chitosan (CS-PLL) and an anionic citraconyl anhydride (CA) modified polylysine side graft for chitosan (CS-PLL-CA). The β-carboxylic amide of CS-PLL-CA is pH-labile and self-cleavable under pH 6 or below. When we mixed the cationic (CS-PLL) and anionic (CS-PLL-CA) peptidosaccharide copolymers, they self-assembled, due to electrostatic charge interactions, into nanomicelles (NMs) with the oppositely charged peptides in the core and the chitosan polysaccharide arms on the shell. The NMs exhibited high hemo- and cytocompatibility (nontoxic) at physiological pH of 7.4, due to the chitosan protection on the shell and charge neutralization on the core. Upon reaching the bacterial infection site, the chitosan shell interacted and accumulated around the bacteria. The bacterial infection sites in the body usually show localized acidity as a result of the combined actions of bacterial metabolism and host immune response, and the pH can decrease to as low as 5.5. At this low pH, the β-carboxylic amide bond of the anionic polypeptide gradually hydrolyzed to expose the initial cationic amine moieties, causing the NMs to ‘decompose’ into individual CS-PLL and ‘spill’ the cationic molecules which then disrupted and killed the bacteria. This ‘smart’ bacteria-recognizing chitosan-decorated nanosystem opens the pathway to explore other anionic and cationic and biocompatible polymers for ‘stealth’ delivery of antimicrobial polypeptide, and ‘on-demand’ recovery of the cationic parts to kill bacteria at infection sites.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Pranantyo, Dicky
Kang, En-Tang
Chan-Park, Mary B.
format Article
author Pranantyo, Dicky
Kang, En-Tang
Chan-Park, Mary B.
author_sort Pranantyo, Dicky
title Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
title_short Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
title_full Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
title_fullStr Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
title_full_unstemmed Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
title_sort smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
publishDate 2021
url https://hdl.handle.net/10356/154042
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