The Design,Synthesis And Gene Transfection Of Cationic Polymer

Because the cationic polymer gene vector has many advantages such as easy preparation,high stability,low immune response,strong plasmid load capability,in gene therapy,so we designed two kinds of different cationic polymeric carrier:gelatin-polyethylene imine polymer carrier containing RGD(GT-PEI)and amino modified controllable regular polymer gene carrier.Gelatin,the denatured protein is obtained either by partial acid or alkaline hydrolysis or by thermal or enzymatic degradation of.Gelatin has a period of arginine,glycine and aspartate(Arg-Gly-Asp)peptide(RGD)which can be combined with integrin on cancer cell surface specificity and RGD can increase cell adhesion,improve cells absorbing.According to this,we added link arms to gelatin and then crosslink different concentrations of PEI,different structure of PEI,different molecular weight of PEI.Finally we prepared 64 kinds cancer targeted GT-PEI polymer carriers.We found the GT-PEI11 has the best transfection efficiency.In A549,B16F10,COST,HEPG2 cells,the transfection efficiency reached 74%?58%?66%?29%.In the cancer cells A549 and B16F10 cells,it has better transfection efficiency which means RGD can target cancer cells.Compared with 25 kda PEI,they have higher transfection efficiency and lower cytotoxicity.It may have a good application prospect in gene delivery.Regular cationic polymer has advantages of regular structure,controlled molecular weight,convenient modification as gene carrier.We used 5-Benzyl L-glutamate N-carboxyanhydride and Furfurylamine to prepare cationic polymer skeleton through ring opening polymerization.Then the product is modified by ethylene diamine,N,N-dimethyl ethylenediamine,1,5-diamino-2-methylpentane,In A549,B16F10,COS7,HEPG2 cells,the transfection efficiency of P6 reached 43%48%53%and 27%.Through experiments,we found that when the regular polymer skeleton has appropriate positive charge,the gene transfection efficiency increased.But if it has too much positive charge,the gene transfection efficiency may decrease and toxicity increased.