Sequence Control as a Powerful Tool for Improving the Selectivity of Antimicrobial Polymers

Abstract

Antimicrobial polymers appear as a promising alternative to tackle the current development of bacterial resistance against conventional antibiotics as they rely on bacterial membrane disruption. This study investigates the effect of segmentation of hydrophobic and cationic functionalities on antimicrobial polymers over their selectivity between bacteria and mammalian cells. Using RAFT technology, statistical, diblock, and highly segmented multiblock copolymers were synthesized in a controlled manner. Polymers were analyzed by HPLC, and the segmentation was found to have a significant influence on their overall hydrophobicity. In addition, the amount of incorporated cationic comonomer was varied to yield a small library of bioactive macromolecules. The antimicrobial properties of these compounds were probed against pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis), and their biocompatibility was tested using hemolysis and erythrocyte aggregation assays, as well as mammalian cell viability assays. In all cases, diblock and multiblock copolymers were found to outperform statistical copolymers, and for polymers with a low content of cationic comonomer, the multiblock showed a tremendously increased selectivity for P. aeruginosa and S. epidermidis compared to its statistical and diblock analogue. This work highlights the remarkable effect of segmentation on both the physical properties of the materials as well as their interaction with biological systems. Due to the outstanding selectivity of multiblock copolymers toward certain bacteria strains, the presented materials are a promising platform for the treatment of infections and a valuable tool to combat antimicrobial resistance.

Quantitative preparation of multiblock glycopolymers bearing glycounits at the terminal segments by aqueous reversible addition–fragmentation chain transfer polymerization of acrylamide monomers

“…Optimizing the conditions for aqueous RAFT polymerization enabled the RAFT terminal to maintain high livingness and the polymers to be prepared in a short period of time. The sequence‐controlled multiblock copolymers by RAFT polymerization were utilized in biological applications, and the influence of the monomer sequence on the function was studied …”

Towards Sequence‐Controlled Antimicrobial Polymers: Effect of Polymer Block Order on Antimicrobial Activity

“…Also, in some antimicrobial polymer studies, the self‐assembly of polymers in solution removes the antimicrobial activities . In previous work,– less hydrophobic monomers were used allowing block structures to maintain antimicrobial efficacy. This suggests that the type of hydrophobic monomers is an important consideration for antimicrobial polymers with clustered/block formations, especially with highly hydrophobic functional groups such as phenylethyl …”

Polymers for Fluorescence Imaging of Formaldehyde in Living Systems via the Hantzsch Reaction

“…[42][43][44][45][46][47][48][49][50][51][52][53][54][55] Recent studies have reported that polymer structures (i.e., sequences and topology structures) remarkably affect the properties or functions of polymers. 53,[56][57][58][59][60] Thus, the future combination of these modern CRP techniques with the method used herein might offer new polymeric probes for the more rapid, more precise detection of FA in biological systems.…”