<br/>Various types of polycations have been design for the purpose of the application as non-viral gene vector. We have investigated the non-viral gene vector based on the molecular design of polycations. We studied for the head-tail type polycations composed of polyamidoamine (PAMAM) dendron head and poly(L-lysine) tail (PAMAM dendron-PLL), in which tertiary amines in the interior of PAMAM dendron head showed buffering effect for endosomal escape and PLL tails formed stable complexes with DNA. To improve the stability of the polyplexes in the presence of serum proteins, PEG chains introduced to the periphery of PAMAM dendron head. The introduction of PEG chains provided not only improvement of stability but also polyplex morphology. Multi-arm PEG structure was constructed through the introduction of PEG chains to PAMAM dendron head, and multi-arm PEG could have effective exclusion volume. Due to large exclusion volume of multi-arm PEG, the polyplex surface was effectively surrounded and the elongated polyplexes, i.e. nanorod and nanofiber, were formed. In this study, the effect of multi-arm PEG density at the polyplex surface was evaluated by the polyplexes prepared using the polycation mixture of PLL homopolymer and nanofiber-forming polymer. The aspect ratio of polyplexes, which determined by AFM observation, could be controlled by changing the mixture ratio of PLL and nanofiber-forming polymer. Importantly the polyplex morphology influenced to cellular uptake and transfection efficiency.

Aspect ratio-controllable polyplexes prepared from poly(L-lysine) terminally bearing multi-arm PEG

255th National Meeting (2018)

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