The Regulation Of Small Size Nanoparticles On The Self-assembly Process Of A?(1-40)Peptides

Alzheimer's disease(AD),as a progressive and irreversible neurodegenerative disease,is characterized by the deposition of A?plaques resulted from the aggregation of A? peptides.Specifically,the aggregation of A? undergoes the transition from monomers,soluble polymer intermediates to insoluble fibers.The A? aggregates have been verified have different degrees of neurotoxicity.The study of effective treatment program has become a challenging task as the incidence of AD increases gradually.So far,a large number of studies have focused on developing the drugs used to regulate the fibrosis process or crack the mature fiber.Among of them,nano-materials provide a good platform for the treatment of AD due to its unique properties(surface modification,large surface area and controllable shape and size).In addition,as a brain disease,the ability to cross the blood-brain barrier(BBB)is another key issue.In response to this problem,some researchers have confirmed that small size nanoparticles have significantly improved BBB capability.Based on the above research background,we synthesized the ultra small size functionalized gold nanoparticles(USGNPs)and polymer nanoparticles(Pdots),and systematically studied the regulation effect of these NPs on A? fibrosis process and neurotoxicity.(1)Firstly,we summarize the pathologic features and the corresponding neurotoxicity.Then the research progress of AD therapy is introduced.(2)The ultra small size gold nanoparticles(USGNPs)were prepared using sodium borohydride reduction method and modified with neurotransmitter dopamine(DA)and its precursor(L-Phe)and phenylalanine,tyrosine(Tyr)by chemical crosslinking reactions.The infrared spectrum(FT-IR)and Zeta potential measurements verified the successful modification process.In addition,the ultraviolet spectrophotometer(UV-Vis),dynamic light scattering(DLS),transmission electron microscope(TEM)characterizations demonstrated that they have the uniform size and good dispersin.Meanwhile,their stability in was tested in buffer solution and cell culture.(3)The regulation effect of these USGNPs on A? fibrils process wasstudied.The thioflavin T fluorescence intensity(ThT),total internal reflection fluorescence microscopy(TIRFM)and transmission electron microscope(TEM)were implemented to test the regulation influence of USGNPs,small molecules and functionalized USGNPs respectively.The interaction mechanism was interpreted.In addition,the cytotoxicity assy(MTT)experiment indicates these USGNPs has good biocompatibility,they can not only regulate A? fibrosis process but also reduce the neurotoxicity.(4)The positively charged polymer nanoparticles(Pdots)were synthesized by using four different ligands.Their particle size,and surface Zeta potential were characterized by DLS,TEM,UV-Vis meseaments.Similarly,ThT,TIRFM and TEM were applied to test the regulation influence of Pdots on fibrosis process.The interaction mechanism was interpreted.Their good biocompatibility was also verified by MTT.