Silver Nanoparticle Conjugated Star PCL-b-AMPs Copolymer as Nanocomposite Exhibits Efficient Antibacterial Properties

The traditional antibiotics have specific intracellular targets and disinfect in chemical ways, and the drug-resistance induced by the antibiotics has grown into an emerging threat. It is urgent to call for novel strategies and antibacterial materials to control this situation. Herein, we report a class of silver-decorated nanocomposite AgNPs@PCL-b-AMPs as potent nanoantibiotic, constructed by ring-opening polymerization of the monomers ε-caprolactone, Z-Lys-N-carboxyanhydrides (NCAs), and Phe-NCAs, then decorated with AgNPs, and characterized by SEM, TEM, and DLS. The biological assays revealed that the nanocomposite possessed strong antibacterial efficacy against both Gram-positive and Gram-negative bacteria including clinical isolated bacteria MRSA, VRE, P. aeruginosa, and K. pneumonia, exhibiting a MIC value range in 2-8 μg/mL. Importantly, the S. aureus and P. aeruginosa treated with the nanocomposite did not show drug-resistance even after 21 passages. Also, in vivo anti-infective assays showed that the nanocomposite was able to effectively kill bacteria in the infected viscera of mice. The study of the sterilization mechanism showed that the nanocomposite exhibited a multimodal antimicrobial mechanism, including irreversibly damaging the membrane structure, making the leakage of intracellular ions and subsequently inducing generation of the reactive oxygen species (ROS), ultimately sterilizing the bacteria. The nanocomposite exhibits effective broad-spectrum antibacterial properties and shows low toxicity to the mammalian cells/animal. Overall, the AgNPs@PCL-b-AMPs gained in this work show great potential as a highly promising antibacterial material for biomedical applications including drug-resistant bacterial infection.