Effect of head size in head-tail-type polycations on their in vitro performances as nonviral gene vectors.

Three kinds of head-tail-type block copolymers composed of polyamidoamine (PAMAM) dendron heads and poly(L-lysine) (PLL) tail blocks (PAMAM dendron-PLL), having PAMAM dendrons with different generations (G2.5-PLL, G3.5-PLL and G4.5-PLL) were synthesized. Some of the dendron heads were located at polyplex surface, and G2.5-PLL and G3.5-PLL could form small polyplexes (less than 150 nm in size). G2.5-PLL and G3.5-PLL polyplexes were taken up into the cells more effectively. PAMAM dendron-PLL that had a larger dendron head could show a more-effective buffering effect. The in vitro performance of the PAMAM dendron-PLL polyplexes was controlled by the balance of cellular uptake and endosomal escape by a buffering effect.