Self-Assembled Borneol-Guanidine-Based Amphiphilic Polymers as an Efficient Antibiofilm Agent

Abstract

Biofilm-associated infections remain a tremendous obstacle to the treatment of microbial infections globally. However, the poor penetrability to a dense extracellular polymeric substance matrix of traditional antibacterial agents limits their antibiofilm activity. Here, we show that nanoaggregates formed by self-assembly of amphiphilic borneol-guanidine-based cationic polymers (BGN<i>x</i>-<i>n</i>) possess strong antibacterial activity and can eliminate mature <i>Staphylococcus aureus</i> (<i>S. aureus</i>) biofilms. The introduction of the guanidine moiety improves the hydrophilicity and membrane penetrability of BGN<i>x</i>-<i>n</i>. The self-assembled nanoaggregates with highly localized positive charges are expected to enhance their interaction with negatively charged bacteria and biofilms. Furthermore, nanoaggregates dissociate on the surface of biofilms into smaller BGN<i>x</i>-<i>n</i> polymers, which enhances their ability to penetrate biofilms. BGN<i>x</i>-<i>n</i> nanoaggregates that exhibit superior antibacterial activity have the minimum inhibitory concentration (MIC) of 62.5 μg·mL^-1 against <i>S. aureus</i> and eradicate mature biofilms at 4 × MIC with negligible hemolysis. Taken together, this size-variable self-assembly system offers a promising strategy for the development of effective antibiofilm agents.