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


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.
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