Gold Nanorods And Antimicrobial Peptides Based Drug Delivery System For Killing Drug-Resistant Bacteria

The misuse and abuse of antibiotics have given rise to a severe problem of drug resistance of bacteria.Solving this problem has been a vitally important task in modern medical arena.In this thesis project,antimicrobial peptides(AMPs)and gold nanorods(AuNRs)were used to fabricate a specific drug delivery system to kill methicilin-resistant staphylococcus aureus(MRSA).On the one hand,AMPs have unique anti-bacterial performance and have less possibility to engender drug resistance of bacteria,which are regarded as a promising substitute of antibiotics.On the other hand,AuNRs equip diverse distinct properties,such as photo-thermal conversion which can be employed for photo-thermal sterilization,besides,AuNRs possess excellent bio-compatibility.Although there is currently much research work using AMPs or AMPs conjugated nanoparticles for antibacterial application,there are still few reports about using AMPs conjugated AuNRs to kill drug-resistant bacteria.We aim to integrate the anti-bacterial activity of AMPs and photo-thermal sterilization of AuNRs to kill drug-resistant bacteria.Firstly,we prepared PEG and BF2b(a type of AMPs)modified AuNRs(AuNR@PEG/BF2b).It was proved that AuNRs were able to dramatically enhance the anti-bacterial effect and cell compatibility of AMPs.The grafting rate of BF2b and PEG on AuNRs was firstly examined.The stability of AuNR@PEG/BF2b was then verified by UV-vis,DLS and TEM methods.The efficiency of photo-thermal conversion of AuNR@PEG/BF2b was subsequently testified.Through MTT assay and hemolytic test,we evaluated the bio-compatibility of AuNR@PEG/BF2b.We also tested the in-vitro and in-vivo anti-bacterial activity of AuNR@PEG/BF2b both in qualitative and quantitative level.We further designed a multi-functional peptides(BrEK)to modify AuNRs(AuNR@BrEK),which exhibited anti-fouling,anti-bacterial and bacteria-responsive activity.Note that this smart system not only acquired bacteria-responsive ability,but also inherited the excellent anti-bacterial activity of AuNR@PEG/BF2b,which helped fulfil their anti-bacterial activity in specific sites.The peptide grafting rate of AuNR@BrEK was firstly characterized.The stability and bacteria-responsive activity of AuNR@BrEK were subsequently examined.The bio-compatibility of AuNR@BrEK was also evaluated by MTT and hemolytic assay.