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Derivatives Of Poly(D,L-aspartic Acid)Used For Gene Delivery

Posted on:2012-03-16Degree:MasterType:Thesis
Country:ChinaCandidate:D J ZhaoFull Text:PDF
GTID:2250330425984065Subject:Chemistry
Abstract/Summary:PDF Full Text Request
Poly-cation materials are the most commonly used non-viral carriers, which condense pDNA through the static electricity function, and then enter the cell. The polyethylenamine (PEI) could effectively protect pDNA from degrade in the transmission process by the nuclease, and achieves the highly effective transfection. It is the result of its unique molecular structure, which makes it has a very strong buffer capacity in the pH=2-10scope. In the past years, we have constructed a series of polymer based on PEI (Mw=600), such as PEI-CyD, PHPA-PEI, Tf-g-PEI, PEG-PEI and so on. They all have highly effective transfection, and lower toxicity. Here, we designed a new polymer based on poly(aspartic acid), which has similar amino composition with PEI. Cytotoxicity changed during the different of amino composition, and so is transfection efficiency.Poly amino acid is often used as gene carriers becauseof its degradability, like lysine, arginine, histidine and so on. Aspartic acid, one kind of alkalinity amino acid, can not used as a gene carrier. Here we modified poly(aspartic acid) with N,N-Dimethyldipropylenetriamine and Bis(3-aminopropyl)amine, and obtained a series of polymer with different amino proportion. The experimental results indicated that they all have very strong pDNA binding ability, and delivery report genes to effectively transfect in cells. The MTT experiment indicated that the cytotoxicity is smaller than PEI-25k far in the concentration of transfection. The transfection experiment showed that they can highly effective expression in COS-7cells, B16BL6cells and Hep G2cells, and PSI-NN’0.85-NN1is the best one.The result showed that change of amino composition effectively adjust the transfection efficiency. And the use of degradable principal chain enhanced the carrier biological compatibility. It provides one kind of mentality for the gene carrier’s construction.
Keywords/Search Tags:Poly(D,L-aspartic
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