The Preparation And Antibacterial Properties Of Biomimetic Peptide-Based Self-Assembled Materials

The rapid development of bacterial resistance to antibiotics makes the therapeutics of bacterial infections a huge challenge.There is an urgent need for a non-traditional strategy to effectively defend against bacterial infection.Defensin is a type of polypeptide that kills microorganisms such as bacteria,fungi or viruses and has antitumor activity.Natural defensins are distributed in almost all biological groups,from plants to lower animals to mammals.They evolved from long-term struggles with diseases and are an important part of their own defense systems.Bionics is a scientific method that mimics the functions and behaviors of biological systems to construct technical systems.This paper used biomimetic strategies to simulate natural defensins for antimicrobial research.Human defensin 6(HD6)is a special antibacterial peptide.Unlike other defensins,it can trap bacterial pathogens by forming a fiber network through self-assembling nanofibers and prevent its invasion rather than in vitro bactericidal activity.Based on the antibacterial strategy of HD6,this paper designed a peptide nanomaterial that realized self-assembly by identifying bacterial surface molecules.The peptide nanomaterial contains three modules:(i)The Bis-Pyrenes(BP)sequence with Aggregation-Induced Emission(AIE)effect can be used as a hydrophobic core in the formation of nanoparticles.When the nanoparticles are formed,the fluorescence signal can be generated with the function of characterizing the state of molecular aggregation and fluorescence imaging of bacteria.(ii)The KLVFF motif originated from A?,a peptide skeleton capable of forming a stable ?-sheet structure by hydrogen bonding.(iii)The targeting peptide sequence RLYLRIGRR,whose target lipoteichoic acid(LTA)is a unique component of Gram-positive bacteria.The designed polypeptide nanomaterial enabled the identification and inhibition of bacterial invasion by different assembly patterns for the treatment of bacterial infections.Firstly,the peptide molecules were successfully synthesized by solid phase synthesis,and the molecular weight of the peptide materials was characterized by time-of-flight mass spectrometry.It is indicated that molecules with the same molecular weight as the target are prepared,and the successful synthesis of the polypeptide nanomaterial is confirmed.Then,nanoparticles were prepared by hydrophobic interaction,which can specifically target Gram-positive bacteria and transform into nanofibers with ?-sheet structure on the surface of bacteria.The recognition of the interaction between the peptide material and the bacteria was confirmed by confocal microscopy.It was found that the peptide material can target bacteria accurately.To further verify its targeting,the peptide material was observed by transmission electron microscopy and scanning electron microscopy.The microscopic morphology after bacterial interaction was observed and it was found that fibrous structures were present on the surface of the bacteria and the bacteria aggregated.The turbidity change after interaction between the polypeptide material and the bacteria was monitored by an ultraviolet-visible spectrophotometer.It was found that the turbidity in the mixed solution was reduced from 2.5 to 0 in two hours.This phenomenon was consistent with the behavior of nanofibers surrounded by bacteria and agglomerated bacteria observed by scanning electron microscopy.Moreover,the nanofibers based on the polypeptide material were effective in preventing the bacteria from invading the normal cells of the human body,and the self-assembly process of the polypeptide material is similar to the working mechanism of the human defensin 6.Finally,it was verified by in vivo experiments that this strategy can be successfully targeted to the surface of S.aureus,and such targeting behavior provided the possibility to identify different kinds of bacteria.At the same time,the muscle infection model and bacteremia model of mice were established.It was found that the polypeptide material can successfully improve the survival rate of bacteremia mice.By quantitative analysis of inflammatory factors in mouse blood,it was found that the polypeptide material reduced the secretion of inflammatory factors.In this paper,the peptide materials with targeting and self-assembly ability were successfully prepared.The nanoparticles were prepared by hydrophobic interaction,and the process of self-assembly and formation of nanofibers was verified and characterized.in-situ self-assembly has been successfully achieved in vivo and has excellent antibacterial properties.