Amphiphilic cationic lipopeptides with RGD sequences as gene vectors.

Two kinds of arginine-rich amphiphilic lipopeptides with hydrophobic aliphatic tails (C(12)GR(8)GDS, LP1 and C(18)GR(8)GDS, LP2) were designed and synthesized as functional gene vectors. With hydrophobic tail modification, these amphiphilic lipopeptides could bind DNA more efficiently and form stable spherical complexes in comparison with the control peptide (AcGR(8)GDS, P1). Moreover, the size and zeta potential results demonstrated the charge density and stability of the vector/DNA complexes could be improved with the increasing length of the aliphatic tails. In vitro transfection experiments showed that LP1 and LP2 could induce much higher gene expression level (luciferase expression) as compared with P1. Due to the incorporation of arginine-glycine-aspartic acid (RGD) sequences which could be specifically recognized by integrins alpha(upsilon)beta(3) and alpha(upsilon)beta(5) over-expressed on cancer cells, these lipopeptides could be specifically recognized by cancer cells, i.e. LP1 and LP2 exhibited relatively higher transfection efficiency in HeLa cell line than that of P2 and P3 without RGD sequence. While the transfection efficiencies of LP2 and P2 were similar in 293T cells. Lipopeptides exhibited very low cell cytotoxicity in both HeLa and 293T cell lines even at high concentration.