Study On Acid-Sensitive Protein Mimicry Based On Poly(amidoamine) Dendrimer

The targeted nanodrug delivery draws great attention because of its good therapeutic results and promising potential applications.However,most of the targeted nanodrug cannot be compared with the nature protein in body such as antibodies in biocompatibility and specificity.It is a far-reaching task to learn protein characteristics and mimic the surface structure in nanodrug design.Dendrimer is widely used in the as targeted nanodrug because of its similar size with protein,numbers of modification sites and internal cavity.In this thesis,we synthesis the acid-sensitive protein mimicry molecule by using the method following:zwitterion was modified on dendrimer surface to mimic the behavior of protein;acid sensitive groups were grafted to change the responsibility in environment.The main contents and conclusions of this dissertation include the following two parts:(1)Polyamidoamine(PAMAM)dendrimer modified with zwitterion containing histidine as zeta-potential adjustor(G5MC-H)was prepared.The reversal of zeta-potential change the affinity between G5MC-H particles and the tumor cell.The results showed that PAMAM particles had strong resistance to cells in physiological pH because of the high negative electricity;and on the contrary,the high affinity to tumour cell membranes in the slightly acidic extracellular pH caused by the positive electricity.In addition,the PAMAM particles showed low toxicity and long blood circulation because of its nonfouling property by modified using zwitterion.(2)Based on the design of G5MC-H,the RGD peptides was add into the targeting system for dual-targeting to integrin-sensitive tumor.The results showed that the G5MC-H-R containing c(RGDfC)has acid sensitivity properties and low cytotoxicity.Although c(RGDfC)has not been able to function as expected in cellular uptake,it can assist in the better distribution of the material inside the tumor tissue and further improve the targeted transport capacity of the vector.