Ciprofloxacin peptide-based nanoparticles confer antimicrobial efficacy against multidrug-resistant bacteria

Abstract

The advent of antibiotics plays a vital role in dealing with the challenges of various bacterial infections, which have saved millions of patients from the brink of death. However, the abuse of antibiotics accelerated the development of bacterial drug-resistance, posing a serious threat to public health. To conquer increasingly severe drug-resistance, the amphiphilic ciprofloxacin peptide-based polymer (PAC) was prepared, which could self-assemble into positively charged nanostructures (PAC-NPs) with a diameter of 300 nm and a zeta potential of +28.6 mV in aqueous solution, confirmed by SEM and DLS. The biological assays displayed that the PAC-NPs possessed broad-spectrum and excellent antibacterial effect against both Gram-positive and Gram-negative bacteria, with an MIC in the range of 1.0–4.0 μg mL⁻¹ and more than 91% sterilization rate. Most importantly, the cationic PAC-NPs did not easily cause antibiotic-resistance and showed low toxicity both in vivo and in vitro. The unique antibacterial mechanism systematically detected by different techniques revealed that the nanoparticles could completely destroy the morphology of bacterial cells, eventually leading to the irreversible apoptosis of bacterial cells, which elucidated why the bacteria were less prone to develop resistance toward PAC-NPs. This study provides a promising strategy by mimicking the structure of AMPs to construct novel bactericidal materials without inducing drug-resistance.