Cholesteroled polymer (Chol-b-Lys)-based nanoparticles (CL-NPs) confer antibacterial efficacy without resistance

It is imperative to develop innovative and efficient antibacterial agents, on account of the mounting prevalence of complicated infections induced by multidrug-resistant bacteria. In this work, Chol-b-Lys nanoparticles (CL-NPs) with a diameter of 304.9 nm were prepared by ring-opening polymerization of the monomers cholesterol-ethylenediamine conjugate (Chol-NH2) and L-Lys-N-carboxyanhydrides (L-Lys-NCAs) and further self-assembly. The nanoparticles exhibited biological activity against the drug-resistant and non-resistant bacteria, including Gram-negative E. coli and Gram-positive B. subtilis, E. faecalis and S. aureus, with a MIC value in the range of 32–2 μg mL−1 and a more than 95% bactericidal rate. Importantly, both bacteria treated with CL-NPs didn’t develop resistance even after their 16th passages. Also, the CL-NPs have low toxicity (32 μg mL−1). The mechanism characterization shows that the positively charged nanoparticles are initially gathered on the surface of bacteria by electrostatic adsorption, changes the membrane permeability, inserts into the lipid bilayer bacteria membrane with cholesterol groups, destroys the membrane structure and results in bacterial apoptosis. This work provides a potential approach by mimicking the structure of cell membrane to develop new bactericidal reagent/nanoparticle materials which is hard to cause resistance.