Broad-Spectrum Antimicrobial Supramolecular Assemblies with Distinctive Size and Shape

Abstract

With the increased prevalence of antibiotic-resistant infections, there is an urgent need for innovative antimicrobial treatments. One such area being actively explored is the use of self-assembling cationic polymers. This relatively new class of materials was inspired by biologically pervasive cationic host defense peptides. The antimicrobial action of both the synthetic polymers and naturally occurring peptides is believed to be complemented by their three-dimensional structure. In an effort to evaluate shape effects on antimicrobial materials, triblock polymers were polymerized from an assembly directing terephthalamide-bisurea core. Simple changes to this core, such as the addition of a methylene spacer, served to direct self-assembly into distinct morphologies-spheres and rods. Computational modeling also demonstrated how subtle core changes could directly alter urea stacking motifs manifesting in unique multidirectional hydrogen-bond networks despite the vast majority of material consisting of poly(lactide) (interior block) and cationic polycarbonates (exterior block). Upon testing the spherical and rod-like morphologies for antimicrobial properties, it was found that both possessed broad-spectrum activity (Gram-negative and Gram-positive bacteria as well as fungi) with minimal hemolysis, although only the rod-like assemblies were effective against Candida albicans.

Controlling macromolecular structures towards effective antimicrobial polymers

“…Another type of biodegradable cationic antimicrobial nanoparticles was synthesized by Hedrick and co-workers [168]. An assembly directing terephthalamide-bisurea core was used to initiate triblock copolymers of lactide and cyclic carbonates.…”

Poly(trimethylene carbonate)-based polymers engineered for biodegradable functional biomaterials

“…Although no report has been published yet, some of the serinol-derived PTMC derivatives ( Figure 3E, F) can be potentially used as polymeric antimicrobials through quaternization and acidolysis of tert-butoxycarbonyl(Boc)-protected side chain affording ammonium salts. 72 Please do not adjust margins Please do not adjust margins Besides the modulation of the primary architecture of the cationic moiety, the introduction of biocompatible biomolecules, 216,218 supramolecular approach, 219 and hydrogelation 220 have also been surveyed to increase and broaden the antimicrobial properties with a low level of hemolytic properties ( Figure 10). In particular, the supramolecular approach raised the importance of the shape of antimicrobials upon the efficacy against some fungi.…”

Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility

“…Recently, several cationic synthetic polymers and peptides have been designed and used as the molecular building blocks to form supramolecular assemblies with tunable, nanostructure-dependent antimicrobial activity. 12, 15, 18, 21, 22 …”