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...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 H2O2 levels.Besides,the representative A1B1C1 networks,composed of polymyxin B1(A1),2-formylphenylboronic acid(B1),and quercetin(C1),inhibit biofilm formation of drug-resistant Escherichia coli,eliminate the mature biofilms,alleviate macrophage inflammation,and minimize the side effects of free polymyxins.Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 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.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.52203184,22275043,51773099,52293380,and 52293383)Startup Fund of Wenzhou Institute,University of Chinese Academy of Sciences(Grant No.WIUCASQD2021022)+1 种基金Key Laboratory of Functional Polymer Materials,Ministry of Education(Grant No.KLFPM202202)Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province(Grant No.2022E10022).
文摘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 H2O2 levels.Besides,the representative A1B1C1 networks,composed of polymyxin B1(A1),2-formylphenylboronic acid(B1),and quercetin(C1),inhibit biofilm formation of drug-resistant Escherichia coli,eliminate the mature biofilms,alleviate macrophage inflammation,and minimize the side effects of free polymyxins.Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 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.
