Synthesis And Application Of Dendrimer Polyamidoamine

Dendrimers are a new class of synthesized macromolecules in the latest twentieth century. They are globular, highly branched, monodispersed macromolecules. The specific structure makes dendrimers suitable for a variety of biomedical applications. Among them the use of dendrimers as a gene delivery system has been of great interest. The first dendrimers that have been thoroughly investigated and received widespread attention are PAMAM dendrimers. The purpose of the research in this paper is the synthesis and modification of PAMAM dendrimers, the biological application of PAMAM interacted with quantum dots, and the preparation and gene delivery research of PAMAM complex with PLGA. The main results are as follows:1. PAMAM dendrimers were synthesized using a conventional two-step iterative procedure: a) double alkylation of -NH2 end groups with methyl acrylate to generate the ester terminating dendrimers, b) amidation of the terminal ester with the corresponding diamine. Half generation PAMAM were separated by the method of colum chromatography with methanol and ethyl acetate as eluents. -0.5 G ~ 4.0 G PAMAM dendrimers thus were synthesized and the properties of their self-fluorescence were investigated. In order to enhance the capability of penetrating the cell membrane and improving the gene transfer efficiency, the periphery of dendrimer had been modified by octadecyl chloride. 3.0 G PAMAM with different periphery hydrophobic long chains were achieved.2. Solvent evaporation method was used to prepare water-soluble, biocompatible QDs nanoparticles through the encapsulation of hydrophobic QDs CdSe/ZnS into ester terminated PAMAM/surfactant nanoparticles. The resulting water-soluble QDs nanoparticles had remained the optical properties of the original hydrophobic QDs. The QDs nanoparticles were regular particles with good morphology (100– 150 nm) and had a good dispersion property, which could be used for bioprobes to mark Hela cells. 3. PAMAM-PLGA nanoparticles were prepared through the solvent diffusion method. The volume ratio of the aqueous to organic phases played an important role in the preparation of the PAMAM-PLGA nanoparticles. The mean size of PAMAM– PLGA nanoparticles was 149.7 nm when the volume ratio of the aqueous to organic phases was 12, and the concentration of surfanctant was 1 %. Nanoparticles prepared in our paper were stable in pH = 7~9 without precipitation.4. PAMAM-PLGA-DNA nanoparticles with different N/P ratio were prepared. Their properties as gene delivery were evaluated using green fluorescence protein pDNA gene as model gene drug. The result of the gene transfer experiment in vitro showed that the DNA gene could be delivered into cells by PAMAM-PLGA nanoparticles, and the efficiency of delivery was higher than that of single 3.0 G PAMAM. The obtained PAMAM-PLGA nanoparticles could express green fluorescence protein, which demonstrated that PAMAM-PLGA nanoparticles could enhance the efficiency of transfer gene.In this paper, the self-fluorescence properties of PAMAM dendrimers were investigated. However, its mechanism needs to be further exploited. In addition, PAMAM-PLGA nanoparticles could increase the gene transfer efficiency compared with single 3.0 G PAMAM, however, the efficiency of PAMAM-PLGA was still lower than that of commercial liposomes. Therefore, we should do further research on it in future.