The Design,Synthesis And Transfection Of Disulfide-containing Polymer

Cationic polymers, as gene carrier alternative to viral gene carrier, have shown great potential in gene therapy. Cationic polymers are able to be combined with specific gene, leading to the formation of gene complexes which could enter into the cell to further complete the gene delivery under the endocytosis. In the paper, we successfully designed two kinds of gene carriers based on cationic polymers:disulfide-containing poly(β-amino ester)s (PBAE) and hydroxylated poly(ethylene imine) (PEI).Disulfide bonds can stay stable in extracellular environment, when exposed to cytoplasm where glutathione (GSH) exists in higher concentration, disulfide can degrade rapidly. In order to design disulfide-containing poly(β-amino ester)s, we introduced the disulfide into diacrylate, which was further used to react with alkamine, leading to the formation of 64 disulfide-containing poly(P-amino ester)s. We assessed them through gene transfection, MTT experiment and so on. we found that four PBAE polymers (SF7-1、SF7-2、SF7-3、SF7-4) showed good transfection expression, their transfection efficiency were respectively 48%、 43%、52%、47% and 56%、60%、52%、49% in A549 and COS7 cells. When compared with commercially available PEI25kDa, they had higher transfection efficiency and lower cytotoxicity, showing great potential in gene delivery.poly(ethylene imine) is one of the most effective non-viral gene carriers based on cationic polymer. In most cases, PEI with high molecular weight has high transfection efficiency, but the accompanying high cytotoxicity, to great extent, limits its application as gene carrier. In the paper, we introduced HEAA in different amount into PEI 1800, implementing the hydroxylation and then the hydroxylated PEI 1800 reacted with degradable cross-linker CBA, leading to the formation of a series of PEI polymers. We found that P5、P8、 P11 and P18 have good transfection expression, in A549 cells and COS7 cells, their transfection efficiency were respectively 35%、42%、40%、36% and 39%、42%、49%、37%. Moreover,P8 and P11,in which 20% hydroxyl was introduced, had an advantage over other samples, demonstrating that moderate hydroxyl could improve the transfection efficiency of PEI polymer.