Amination Of Poly(acrylic Acid)and Its Gene Delivery Activity

Gene therapy as a new type of medical technology has great application prospects in the treatment of cancer and other diseases,attracting the attention of many researchers.However,due to the high toxicity,low transfection rate and other issues of the delivery systems,gene therapy has been greatly limited in clinical applications.Therefore,the development of an effective gene carrier has attracted more and more attention of the researchers.Cationic macromolecules are among the most widely researched gene carriers.Due to their high toxicity and low transfection efficiency,various modifications have been conducted by the researchers.Changing the type of amine is one of the most important ways.In this paper,we investigated the effects of different amine types on the biological activity as the gene carriers.In this paper,using poly(acrylic acid)as the starting material,we conjugated the aliphatic chain of primary and alanine on the a-amino through the amide reaction,and by changing the ratio of two amino,four polymers which are named PALAO,PALA1,PALA2 and PALA3 were synthesized.We identified the final structure of the polymerds by characterization of 1H-NMR,13C-NMR and mass spectra.The molecular weight of the synthesized polymers are about 28,000,and the particle size are in accordance with the optimal particle size as the gene carrier and have a positive zeta potential,which are obtained by GPC,DLS and zeta potential.Acid-base titration experiments show that the four polymers have a good buffer capacity.Then,the bioactivities of the polymers were investigated by agarose gel electrophoresis,cytotoxicity assay,plasmid transfection,siRNA transfection and confocal experiments.The results showed that the four polymers had good biological activity as gene vector.Compared with ?-amino groups on alanine,the primary amine on the aliphatic chain have better cell transfection effect and cell penetrating ability,but it has obvious cytotoxicity.In summary,we have successfully carried out amino acidification of poly(acrylic acid)with different amino groups and discussed the activity of different kinds of amine-functionalized poly(acrylic acid)as gene carriers,which provided the basis for the study of gene vector modification in accordance with.