Issue 5, 2021

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

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 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.

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

Supplementary files

Article information

Article type
Paper
Submitted
17 aug 2020
Accepted
09 nov 2020
First published
07 jan 2021
This article is Open Access
Creative Commons BY license

Biomater. Sci., 2021,9, 1627-1638

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

D. Pranantyo, E. Kang and M. B. Chan-Park, Biomater. Sci., 2021, 9, 1627 DOI: 10.1039/D0BM01382J

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