Study On Antibacterial Activity Of Antimicrobial Peptide-modified Silver Nanoparticles

Objective: Nanoparticulate silvers(AgNPs),a powerful and promising bactericide,have limited application due to its toxicity.To improve the antibacterial activity and the applicability,AgNPs were modified with multiple-function peptide(MFP)using physical interaction to exert the synergetic therapeutic effect and inflammation targeting.Methods: MFP was comprised of N-acetyl-proline-glycine-proline(N-Ac-PGP),polyethyl eneglycol(PEG),enzyme-sensitive-peptide(ESP)and Tachyplesin-1.Then MFP was assembled with AgNPs by physical interaction(electrostatic interaction).The structure of MFP@AgNPs was characterized by UV-vis spectrophotometer,zeta potential analysis,FI-IR,and circular dichroism(CD)spectroscopy.The morphology of MFP@AgNPs was detected by TEM.MIC and MBC values of MFP@AgNPs were determined by the broth dilution method and inhibition rate of killing,respectively.Time-dependent killing kinetic profiles was used to observe the bactericidal effect of MDR-AB.The antibacterial mechanism was analyzed by SEM and the change of fluorescence intensity of PI.The biocompatibility was determined by cytotoxic and hemolysis rate.The drug resistance tendency of MDR-AB was examined by detecting MIC of 20 generations.Finally,in vivo antibacterial effect of MFP@AgNPs against MDR-AB was evaluated in pneumonia mice model.Results: The characterization results proved the successful synthesis of MFP@AgNPs.MIC and MBC values showed that MFP@AgNPs had good antibacterial activity against Gram-negative,Gram-positive bacteria and even MDR-AB.MFP@AgNPs can rapidly destruct the bacterial biofilm and kill MDR-AB at a concentration of 6 μg/mL without drug resistance.In addition,MFP@AgNPs had no cytotoxicity to HUVEC and red blood cells.For treatment on pneumonia mice,MFP@AgNPs can enhance the antibacterial activity of AgNPs in vivo and have a good accumulation in the inflammation tissue.Conclusion: We have successfully designed and constructed MFP@AgNPs delivery system in this study.MFP@AgNPs showed low toxicity,inflammation targeting,and improved antibacterial activity in vitro and in vivo.This delivery system would provide a safe and effective choice for the treatment of drug-resistant bacteria...