Biocompatible cationic polypeptoids with antibacterial selectivity depending on hydrophobic carbon chain length

The overuse of antibiotics has triggered a new infection crisis and natural antimicrobial peptides (AMPs) have been extensively studied as an alternative to fight microorganisms. Polypeptoids, or polypeptide-biomimetics, offer similar properties to polypeptides and a highly tunable structure that has been synthesized by various methods such as ring opening polymerization (ROP) using N-carboxyanhydride monomers. Simultaneous high antibacterial activity and biocompatibility of a structure by efficient synthesis is desired in the application of those materials. Herein, a series of cationic polypeptoids (PNBs) with variable side chain lengths was obtained by introducing positive charges to the main chain in one step and preserving the backbone structure, namely polypeptoids (PNBM, PNBE, PNBB) with different end groups (methyl (M), ethyl (E), butyl (B)). To address the issue of infection in interventional biomedical implants, we report cost-effective modified polyurethane (PU) films (PU-PNBM, PU-PNBE, PU-PNBB) as physical-biological synergistic antibacterial surfaces that overcome problems such as steric hindrance and the solubility of the materials. Antibacterial selectivity was achieved by regulating the different side chain lengths. When methyl and ethyl were used as hydrophobic side chains, they can only selectively kill Gram-positive Staphylococcus aureus. PNBB, the most hydrophobic and with a butyl side chain can kill both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and inhibit the growth of bacterial biofilms. Effective in both solution and modified substrate, its biocompatibility is not compromised while the antibacterial properties are substantially improved. Furthermore, PU-PNBB films demonstrated their potential in vivo antimicrobial efficiency in a model of S. aureus infection established on mouse skin. The synthesis route and the surface modification strategies are convenient, providing a solution to the problem of poor biocompatibility in antimicrobial surface applications and a strategy for the use of peptide polymers for targeted therapy after specific infections in the biomedical field.