Aggregation of Cationic Amphiphilic Block and Random Copoly(vinyl ether)s with Antimicrobial Activity.

Kazuma Yasuhara,Yukari Oda,Takahiro Sato,Shokyoku Kanaoka,Kenichi Kuroda,Sadahito Aoshima

doi:10.3390/polym10010093

Abstract

In this study, we investigated the aggregation behaviors of amphiphilic poly(vinyl ether)s with antimicrobial activity. We synthesized a di-block poly(vinyl ether), B3826, composed of cationic primary amine and hydrophobic isobutyl (iBu) side chains, which previously showed antimicrobial activity against Escherichia coli. B3826 showed similar uptake behaviors as those for a hydrophobic fluorescent dye, 1,6-diphenyl-1,3,5-hexatriene, to counterpart polymers including homopolymer H44 and random copolymer R4025, indicating that the iBu block does not form strong hydrophobic domains. The cryo-TEM observations also indicated that the polymer aggregate of B3826 appears to have low-density polymer chains without any defined microscopic structures. We speculate that B3826 formed large aggregates by liquid-liquid separation due to the weak association of polymer chains. The fluorescence microscopy images showed that B3826 bonds to E. coli cell surfaces, and these bacterial cells were stained by propidium iodide, indicating that the cell membranes were significantly damaged. The results suggest that block copolymers may provide a new platform to design and develop antimicrobial materials that can utilize assembled structures and properties.

Highlights

The emergence of drug-resistant bacteria poses a serious threat to human health [1,2,3], as the number of treatment options for bacterial infections is significantly reduced
We studied the aggregation behaviors of amphiphilic poly(vinyl ether)s with antimicrobial activity using fluorescent dye, DPH uptake assay, and fluorescent microscopy
The results results of the DPH uptake experiments indicated that the hydrophobic side chains of our polymers of the DPH uptake experiments indicated that the hydrophobic side chains of our polymers may may not form microscopic strong hydrophobic domains

Summary

Introduction

The emergence of drug-resistant bacteria poses a serious threat to human health [1,2,3], as the number of treatment options for bacterial infections is significantly reduced. One recent strategy is to design synthetic polymers to mimic the structural features and functions of host-defense antimicrobial peptides (AMPs) found in the innate immune system [4,5], which act directly by disrupting bacterial cell membranes. Antimicrobial (co)polymers have cationic and hydrophobic moieties in their side chains to mimic the cationic amphiphilicity of AMPs, which govern the bacterial selectivity and membrane-disrupting. It has been previously demonstrated that the antimicrobial activity of polymers and their toxicity to human cells can be controlled by modulating key structural parameters, including compositions of cationic and hydrophobic monomers [8,9,10,11], molecular weight [11,12], the hydrophobicity of side chains [13], and the type of cationic charge [14]

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Results

Conclusion