TAT-modified self-assembled cationic peptide nanoparticles as an efficient antibacterial agent

Abstract

The increasing emergence of drug resistant pathogenic bacteria poses a great challenge to clinical therapy and a threat to public health. Cationic peptides have received great attention for their unique antibacterial mechanism and ability to combat drug-resistant bacteria. In this study, we designed a TAT-modified cationic peptide PA-28 which self-assembled into nanoparticles of about 150 nm. These nanoparticles showed strong antimicrobial activities against both gram-positive and gram-negative bacteria, including drug-resistant bacteria. They were more potent than the unassembled counterpart peptide nonalysine (K9). Their antibacterial mechanism of directly destructing bacterial wall/membrane reduces the possibility of developing bacterial resistance. In vivo anti-infective experiments showed that these nanoparticles were able to penetrate the blood–brain barrier to inhibit bacterial growth in infected brains of rats. In addition, these nanoparticles induced low hemolysis below the minimum inhibitory concentration. Therefore, the peptide designed in this study is a promising and efficient antibacterial agent against bacterial infections.