Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides

: Lin Caihong, Ma Zunwei, Gao Yunpeng, Le Mengqi, Shi Zhifeng, Qi Dawei, Ma Jian-Chao, Cui Zhong-Kai, Wang Lin, Jia Yong-Guang

Publisher: AMER CHEMICAL SOC

: 2023

: ACS Applied Materials and Interfaces

: ACS APPLIED MATERIALS & INTERFACES

: ACS APPL MATER INTER

: 15

: 28

: 33444

: 33456

: 13

: 1944-8244

: 1944-8252

DOI: https://doi.org/10.1021/acsami.3c06424

: https://pubs.acs.org/doi/10.1021/acsami.3c06424

Antibiotic-resistant bacterial infections have led toan increaseddemand for antibacterial agents that do not contribute to antimicrobialresistance. Antimicrobial peptides (AMPs) with the facially amphiphilicstructures have demonstrated remarkable effectiveness, including theability to suppress antibiotic resistance during bacterial treatment.Herein, inspired by the facially amphiphilic structure of AMPs, thefacially amphiphilic skeletons of bile acids (BAs) are utilized asbuilding blocks to create a main-chain cationic bile acid polymer(MCBAP) with macromolecular facial amphiphilicity via polycondensationand a subsequent quaternization. The optimal MCBAP displays an effectiveactivity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superiorbactericidal stability in vitro, and potent anti-infectious performancein vivo using the MRSA-infected wound model. MCBAP shows the low possibilityto develop drug-resistant bacteria after repeated exposure, whichmay ascribe to the macromolecular facial amphiphilicity promotingbacterial membrane disruption and the generation of reactive oxygenspecies. The easy synthesis and low cost of MCBAP, the superior antimicrobialperformance, and the therapeutic potential in treating MRSA infectionaltogether demonstrate that BAs are a promising group of buildingblocks to mimic the facially amphiphilic structure of AMPs in treatingMRSA infection and alleviating antibiotic resistance.