Antimicrobial peptides (AMPs) have been attracting much attention due to their excellent antimicrobial efficiency and low rate in driving antimicrobial resistance (AMR), which has been increasing globally to alarming levels. Conjugation of AMPs into functional polymers not only preserves excellent antimicrobial activities but reduces the toxicity and offers more functionalities, which brings new insight toward developing multifunctional biomedical materials such as hydrogels, polymer vesicles, polymer micelles, and so forth. These nanomaterials have been exhibiting excellent antimicrobial activity against a broad spectrum of bacteria including multidrug-resistant (MDR) ones, high selectivity, and low cytotoxicity, suggesting promising potentials in wound dressing, implant coating, antibiofilm, tissue engineering, and so forth. This Perspective seeks to highlight the state-of-the-art strategy for the synthesis, self-assembly, and biomedical applications of AMP-polymer conjugates and explore the promising directions for future research ranging from synthetic strategies, multistage and stimuli-responsive antibacterial activities, antifungi applications, and potentials in elimination of inflammation during medical treatment. It also will provide perspectives on how to stem the remaining challenges and unresolved problems in combating bacteria, including MDR ones.

Periodontitis is a common disease caused by plaque biofilms, which are important pathogenic factors of many diseases and may be eradicated by antibiotic therapy. However, low-dose antibiotic therapy is a complicated challenge for eradicating biofilms as hundreds (even thousands) of times higher concentrations of antibiotics are needed than killing planktonic bacteria. Polymer vesicles may solve these problems via effective antibiotic delivery into biofilms, but traditional single corona vesicles lack the multifunctionalities essential for biofilm eradication. In this paper, we aim to effectively treat biofilm-induced periodontitis using much lower concentrations of antibiotics than traditional antibiotic therapy by designing a multifunctional dual corona vesicle with intrinsic antibacterial and enhanced antibiotic delivery capabilities. This vesicle is co-assembled from two block copolymers, poly­(ε-caprolactone)-block-poly­(lysine-stat-phenylalanine) [PCL-b-P­(Lys-stat-Phe)] and poly­(ethylene oxide)-block-poly­(ε-caprolactone) [PEO-b-PCL]. Both PEO and P­(Lys-stat-Phe) coronas have their specific functions: PEO endows vesicles with protein repelling ability to penetrate extracellular polymeric substances in biofilms (“stealthy” coronas), whereas P­(Lys-stat-Phe) provides vesicles with positive charges and broad spectrum intrinsic antibacterial activity. As a result, the dosage of antibiotics can be reduced by 50% when encapsulated in the dual corona vesicles to eradicate Escherichia coli or Staphylococcus aureus biofilms. Furthermore, effective in vivo treatment has been achieved from a rat periodontitis model, as confirmed by significantly reduced dental plaque, and alleviated inflammation. Overall, this “stealthy” and antibacterial dual corona vesicle demonstrates a fresh insight for improving the antibiofilm efficiency of antibiotics and combating the serious threat of biofilm-associated diseases.

Traditional antibiotics usually sterilize in chemical ways, which may lead to serious drug resistance. By contrast, peptide-based antibacterial materials are less susceptible to drug resistance. Herein we report the preparation of an antibacterial peptide-based copolymer micelle and the investigation of its membrane-penetration antibacterial mechanism by transmission electron microscopy (TEM). The copolymer is poly(l-lactide)-block-poly(phenylalanine-stat-lysine) [PLLA-b-poly(Phe-stat-Lys)], which is synthesized by ring-opening polymerization. The PLLA chains form the core, whereas the polypeptide chains form the coronas of the micelle in aqueous solution. This micelle boasts excellent antibacterial efficacy against both Gram-positive and Gram-negative bacteria. Furthermore, TEM studies clearly reveal that the micelles pierce and then destroy the cell membrane of the bacteria. We also compared the advantages and disadvantages of two general methods for measuring the Minimal Inhibitory Concentration (MIC) values of antibacterial micelles. Overall, this study provides us with direct evidence for the antibacterial mechanism of polypeptide-based micelles and a strategy for synthesizing biodegradable antibacterial nanomaterials without antibiotic resistance.

Intrinsically antibacterial polymersomes loaded with antibiotics were incorporated into hydrogels, exhibiting quick and long-acting antibacterial activity.