alpha-amino acid pendant polymers as endosomal pH-responsive gene carriers

作者：Wada Takuya; Kano Arihiro; Shimada Naohiko; Maruyama Atsushi^*

来源：Macromolecular Research, 2012, 20(3): 302-308.

DOI：10.1007/s13233-012-0057-7

• alpha-amino acids
• transfection
• polyplex
• pH-responsiveness
• lysosomotropic activity

In order to prepare gene carriers responsive to an endosomal pH, amino groups of linear poly(allylamine) (PAA) or poly(L-lysine) (PLL) were coupled with a-carboxyl groups of alpha-amino acids (Gly, His, Lys, Arg, and Orn). Acid-base titration indicated that Lys-, Arg-, and Orn-pendant polymers had both strongly basic groups and endosomal pH-responsive alpha-amino groups. These polymers, like PAA and PLL, formed stable complexes with DNA. Lys-, Arg-, and Orn-pendant polymers were effective transfection reagents independent of the backbone polymers. The pH-responsive alpha-amino groups enhanced transfection activity as shown by the observation that acetylation of the alpha-amino group resulted in a considerable loss in transfection activity. These results strongly suggested a lysosomotropic activity of the alpha-amino groups. Among the alpha-amino acid-pendant polymers tested, the Orn-pendant polymer exhibited the highest transfection activity/toxicity index. Since PLL with alpha-amino acid-pendants is composed of naturally occurring amino acids, it is expected to be biodegradable, and these reagents have promise as gene carriers.

• 出版日期2012-3