Long circulation of intravenously administered plasmid DNA delivered with dendritic poly(L-lysine) in the blood flow.

We previously showed that dendritic poly(L-lysine) of the 6th generation (KG6) had high transfection ability without significant cytotoxicity in vitro. Here, to evaluate the potential of KG6 as a nonviral gene carrier that works in vivo, we investigated the biodistribution of plasmid DNA delivered with KG6 in mice after intravenous administration, in comparison with DOTAP/Chol liposomes and PEI. Southern blotting analysis revealed that plasmid DNA complexes with KG6 at a C/A ratio of 8.0 circulated in the blood for 3 h after intravenous injection. The amounts of plasmid DNA in the liver gradually decreased. In tumor-bearing mice, plasmid DNA injected with KG6 was observed in the tumor at 60 min after the intravenous injection, while no DNA was present in the tumor using DOTAP/Chol liposomes. The stealth character of DNA complexes with KG6 in the blood would cause an enhanced permeability and retention (EPR) effect in the tumor. KG6 is expected to be a promising candidate that enables functional gene delivery in vivo.