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Title: Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications
Authors: Pranantyo, Dicky 
Kang, En-Tang 
Chan-Park, Mary B.
Issue Date: 1-Jan-2021
Publisher: Royal Society of Chemistry
Citation: Pranantyo, Dicky, Kang, En-Tang, Chan-Park, Mary B. (2021-01-01). Smart nanomicelles with bacterial infection-responsive disassembly for selective antimicrobial applications. Biomaterials Science 9 (5) : 1627-1638. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 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 ?-poly(l)lysine side-grafted chitosan (CS-PLL) and an anionic citraconyl anhydride (CA) modified polylysine side graft for chitosan (CS-PLL-CA). The ?-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 ?-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. © The Royal Society of Chemistry.
Source Title: Biomaterials Science
ISSN: 2047-4830
DOI: 10.1039/d0bm01382j
Rights: Attribution 4.0 International
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