Studies On Preparation And Application Of Poly(Propylene Imine) Dendrimer As Gene Vector

Gene therapy, the treatment of diseases by transferring normal or remedial gene into the target cells, is regarded as a promising area in medicine. The greatest obstacle of the successful realization of gene therapy is deficient in efficient, non-toxic gene carriers. Cationic polymer gene vector enjoys a high profile due to the safety and nonimmunogenity.Dendrimers have steadily grown in the past decade as new non-virus gene vectors. It is capable of binding DNA by the electrostatic attraction between the cationic charges on the dendrimer and the negative charges on DNA, and protecting DNA from degradation by intracellular enzymes.In the family of dendrimers, poly(propylene imine) dendrimer(PPI) has been synthesized successfully. Synthesis and modification of PPI dendrimer with mPEG, preparation of PPI/DNA complex and investigation of cytotoxity of 2.0G PPI dendrimer are reported in this thesis. The PPI dendrimer with relatively perfect structure is prepared. The side reaction is suppressed to a considerable degree and even eliminated by optimizing reaction conditions, such as raising the reaction temperature and the concentration of reactants, choosing Urushibara-Co as catalyst and dioxane as solvent. Infrared spectrum and titration result indicate that 1.0G and 2.0G PPI dendrimers obtained under the hydrogenation conditions contain higher primary amine. 1HNMR data shows that the structure of low generation PPI dendrimer is perfect. 2.0G PPI dendrimer is modified with malemidyl -N- hydroxy succinimidyl poly(ethylene glycol) (NHS-PEG-MAL) (MW 2000). The data of infrared spectrum and 1HNMR identifies the structure of mPEG-PPI. The study of PPI/DNA complex and cytotoxity of 2.0G PPI dendrimer demonstrates that 2.0G PPI dendrimer is capable of condensing DNA and the cytotoxicity is fairly high, while the modification with PEG of PPI can significantly suppress the cytotoxicity.