Antibacterial Copolypeptoids with Potent Activity against Drug Resistant Bacteria and Biofilms, Excellent Stability, and Recycling Property

Abstract The preparation of a type of innovative cationic copolypeptoid antimicrobials containing various hydrophobic moieties that resemble both structure and membrane‐lytic antibacterial mechanism of natural antimicrobial peptides (AMPs) is reported. By finely tuning the hydrophilic/hydrophobic balance, the polypeptoids exhibit a wide spectrum of antibacterial activity against both Gram‐positive bacteria and Gram‐negative bacteria with the lowest minimum inhibitory concentration (MIC) at only 2 µg mL −1 , whereas they also show low haemolytic properties. In particular, high selectivity (>128) is achieved from the polymers with butyl moieties. Moreover, the polypeptoids can readily inhibit the formation of biofilms and effectively eradicate the bacteria embedded in the mature biofilms, which is superior to many natural AMPs and vancomycin. Unlike conventional antibiotics, the polypeptoids possess potent activity against drug‐resistant bacteria without visible resistance development after repeated usage. Notably, the polypeptoid antimicrobials not only have inherently fast bactericidal properties and excellent stability against incubation with human plasma, but also show excellent in vivo antibacterial effect. The prepared antimicrobials, coated onto magnetic nanospheres show recycling properties and enhanced antibacterial activity as combined with near‐infrared (NIR)‐induced photothermal antibacterial therapy.