| 초록 |
We designed a novel type of argininie-rich dendrimer, the structure of which is based on the well-defined dendrimer, poly(amidoamine)dendrimer (PAMAM). Further characterization was performed to prove that the polymer is a potent nonviral gene delivery carrier. The primary amines located on the surface of PAMAM were conjugated with L-arginine to prepare L-arginine-grafted-PAMAM dendrimer (PAMAM-Arg). For comparison, L-lysine-grafted-PAMAM dendrimer (PAMAM-Lys) was also prepared and compared as control reagent. The polymers were found to self-assemble electrostatically with plasmid DNA, forming nanometer-scale complexes. From dynamic light scattering experiments, the mean diameter of the polyplexes was observed to be around 200 nm. It was also described that the PicoGreen reagent could be used as an efficient probe for the complex formation of polymers with plasmid DNA. The complex composed of PAMAM-Arg/DNA showed increased gene delivery potency compared to native PAMAM dendrimer and PAMAM-Lys. The cytotoxicity and transfection efficiency for 293, HepG2, and Neuro 2A cells was measured in comparison with PEI and PAMAM. In addition, transfection experiments were also performed for primary rat vascular smooth muscle cells and PAMAM-Arg showed much enhanced transfection efficiency. These findings suggest that the L-arginine-grafted-PAMAM dendrimer possesses a potential to be a novel gene delivery carrier for gene therapy. |
