Dynamic covalent nano-networks comprising antibiotics and polyphenols orchestrate bacterial drug resistance reversal and inflammation alleviation.

Li, Yuanfeng; Piao, Yin-Zi; Chen, Hua; Shi, Keqing; Dai, Juqin; Wang, Siran; Zhou, Tieli; Le, Anh-Tuan et al. · Bioact Mater · 2023

basic_science · Level V

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Abstract

New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms. This work reports the facile synthesis of antimicrobial dynamic covalent nano-networks (aDCNs) composing antibiotics bearing multiple primary amines, polyphenols, and a cross-linker acylphenylboronic acid. Mechanistically, the iminoboronate bond drives the formation of aDCNs, facilitates their stability, and renders them highly responsive to stimuli, such as low pH and high H<sub>2</sub>O<sub>2</sub> levels. Besides, the representative <b>A1B1C1</b> networks, composed of polymyxin B1(<b>A1</b>), 2-formylphenylboronic acid (<b>B1</b>), and quercetin (<b>C1</b>), inhibit biofilm formation of drug-resistant <i>Escherichia coli</i>, eliminate the mature biofilms, alleviate macrophage inflammation, and minimize the side effects of free polymyxins. Excellent bacterial eradication and inflammation amelioration efficiency of <b>A1B1C1</b> networks are also observed in a peritoneal infection model. The facile synthesis, excellent antimicrobial performance, and biocompatibility of these aDCNs potentiate them as a much-needed alternative in current antimicrobial pipelines.