Constructing Functionalized Liposome Nanomaterials Applied In Inhibiting Amyloid Peptide Aggregation

Alzheimer’s disease is a neurodegenerative disease.The misfolding and selfassembly of amyloid-β(Aβ)is one of the causes of Alzheimer’s disease(AD).Studies have shown that Aβ is easy to aggregate,forming Aβ aggregates with β-sheet structure,and causing neurotoxicity.Therefore,the research on Aβ as a therapeutic target has become a hot spot of concern,and it is urgent to find materials to inhibit the aggregation of amyloid peptides.The existing inhibitors mainly include small molecule inhibitors,polyoxometallates,nanoparticles,etc.but their biocompatibility is poor.In recent years,some peptide inhibitors have been reported in the literature.The peptide inhibitors have good biocompatibility.However,there are some shortcomings.Small-molecule peptides are easily degraded in the body,and at the same time,the inhibition efficiency is limited.How to improve the stability of the peptides and improve the inhibitory effect on the aggregation of amyloid peptides is very important.In this paper,functionalized liposome nanomaterials were prepared and their inhibitory effects on the aggregation of amyloid Aβ42 were studied,which provides a potential method for the treatment of Alzheimer’s disease.The specific research content is as follows:1)Liposomes are used to construct functionalized nanomaterials.Liposomes are an artificial cell membrane with simple preparation process,good biocompatibility,and low cytotoxicity.The US FDA has approved DSPE-2000 and M-E5 phospholipids as medical excipients,which are good drug carrier materials.Construct functional nanomaterials to combine liposomes with drug carrier function and the KLVFF polypeptide sequence derived from the amyloid polypeptide Aβ42 itself,which is often used to identify and inhibit the aggregation of Aβ42.This paper has found a kind of fusion peptide,α-peptide,which is a functional peptide that is often used for membrane fusion.The α-peptide and KLVFF are connected through the peptide linker sequence GSG to form a functional peptide,which realizes the functionality The stable combination of peptides and DOPC liposomes constructs a functionalized liposome nanomaterial with good biocompatibility.2)On the basis of the previous chapter,the effect of functionalized liposome nanomaterials on inhibiting the aggregation of amyloid Aβ42 and reducing its cytotoxicity was studied.The functionalized liposome nanomaterials and amyloid peptide Aβ42 were incubated together,and the experimental characterization and analysis were performed using transmission electron microscopy,atomic force microscope,and microplate reader.The results show that functional liposome nanomaterials have a certain inhibitory effect on the aggregation of amyloid Aβ42.At the same time,a cytotoxicity test was carried out using nerve cell PC12,indicating that functional liposome nanomaterials can inhibit the cytotoxicity of amyloid Aβ42.3)Functionalized liposome nanomaterials were used to coat Rose Bengal(RB)to prepare functionalized liposome nanocomposites.The amyloid peptide Aβ42 and the composite material were mixed and incubated under LED light irradiation,and the inhibitory effect was studied by fluorescence spectrophotometer,transmission electron microscope,and atomic force microscope.It was found that the functionalized nanoliposomes coated with rose bengal(RB)had a dual inhibitory effect on the aggregation of amyloid Aβ42,which achieved the inhibitory effect of inhibiting the aggregation of amyloid Aβ42 at low doses.