Antimicrobial Nanostructured Assemblies with Extremely Low Toxicity and Potent Activity to Eradicate Staphylococcus Aureus Biofilms

Abstract

Self‐assembled cationic polymeric nanostructures have been receiving increasing attention for efficient antibacterial agents. In this work, a new type of antibacterial agents is developed by preparing pH‐dependent nanostructured assemblies from cationic copolypeptoid poly(N‐allylglycine)‐b‐poly(N‐octylglycine) (PNAG‐b‐PNOG) modified with cysteamine hydrochloride ((PNAG‐g‐NH2)‐b‐PNOG) driven by crystallization and hydrophobicity of the PNOG blocks. Due to the presence of confined domains arising from crystalline PNOG, persistent spheres and fiber‐like assemblies are obtained from the same polymer upon a heating‐cooling cycle. This allows for direct comparison of antimicrobial efficiency of nanostructured assemblies with various morphologies that are otherwise similar. Both nanostructured assemblies exhibit extremely low toxicity to human red blood cells, irrespective of the presence of the hydrophobic block. Enhanced antimicrobial performance of the fiber‐like micelles compared to the spheres, which result in high selectivity of the fibers, is shown. Notably, the fiber‐like micelles show great efficacy in inhibition of the Staphylococcus aureus (S. aureus) biofilm formations and eradication of the mature biofilms, superior to vancomycin. The micelles also show potent in vivo antimicrobial efficacy in a S. aureus infection mouse skin model. With a systematic study, it is demonstrated that both micelles kill the bacteria through a membrane disruption mechanism. These results imply great potential of polypeptoid assemblies as promising excellent candidates for antibacterial treatment and open up new possibilities for the preparation of a new generation of nanostructured antimicrobials.

Synthesis and anti-infective potency study of a Ru-based complex bearing benzonitrile against Staphylococcus aureus

“…Secondly, the anti-infective efficacy of RuBZ was further evaluated through a mouse skin infection model. 49 First, a circular wound was cut on the back of the mice and the S. aureus were added onto the surface to induce inflammation (Fig. 10(A)).…”

Chiral supramolecular nanomaterials: From chirality transfer and amplification to regulation and applications

“…Sun et al created a group of diblock copolypeptoids (poly( N ‐allylglycine)‐ g ‐NH 2 )‐ b ‐poly( N ‐octylglycine) through ring‐opening polymerization and postpolymerization functionalization. [ 171 ] The copolypeptoids exhibit the capacity to undergo self‐assembly into both fibrous and spherical micellar structures in aqueous environments, which is influenced by the pH conditions. The assemblies demonstrate remarkable antimicrobial efficacy due to the presence of amine groups.…”

pH Window for High Selectivity of Ionizable Antimicrobial Polymers toward Bacteria

“…Drug-resistant bacteria pose an increasingly serious threat to human health. − Antimicrobial polymers are substances comprising positively charged and hydrophobic residues in an amphiphilic structure that exhibits great potential for treating drug-resistant bacteria. − Antimicrobial polymers chiefly kill bacteria via membranolytic mechanisms. − They contact the negatively charged bacterial membrane through electrostatic interactions, consequently inserting into the phospholipid bilayer of the bacterial cell membrane via hydrophobic interactions, destabilizing and damaging the membrane. − This membranolytic mechanism can efficiently kill drug-resistant bacteria with a low tendency of inducing drug resistance. − However, antimicrobial polymers can also show considerable toxicity toward normal mammalian cells, and designing selective antimicrobial polymers that exhibit relatively low toxicity toward normal tissues/cells is a key challenge. − …”