Facially Amphiphilic Skeleton-Derived Antibacterial Cationic Dendrimers.

It is urgent to develop biocompatible and high-efficiency antimicrobial agents since microbial infections have always posed serious challenges to human health. Herein, through the marriage of facially amphiphilic skeletons and cationic dendrimers, high-density positively charged dendrimers D-CA 6 -N + (G2) and D-CA 2 -N + (G1) were designed and synthesized using the "branch" of facially amphiphilic bile acids, followed by their modification with quaternary ammonium charges. Both dendrimers could self-assemble into nanostructured micelles in aqueous solution. D-CA 6 -N + displays potent antibacterial activity against Staphylococcus aureus and Escherichia coli , with minimum inhibitory concentrations (MICs) as low as 7.50 and 7.79 μM, respectively, and has an evidently stronger antibacterial activity than D-CA 2 -N + . Moreover, D-CA 6 -N + can kill S. aureus faster than E. coli . The facial amphiphilicity of the bile acid skeleton facilitates the selective destruction of bacterial membranes and endows dendrimers with negligible hemolysis and cytotoxicity even under a high concentration of 16× MIC. In vivo studies show that D-CA 6 -N + is much more effective and safer than penicillin G in treating S. aureus infection and promoting wound healing, which suggests facially amphiphilic skeleton-derived cationic dendrimers can be a promising approach to effectively enhance antibacterial activity and biocompatibility of antibacterial agent, simultaneously.