Kawano Takahito, Okuda Tatsuya, Aoyagi Haruhiko, Niidome Takuro
Department of Materials Science, Graduate School of Science and Technology, Nagasaki University, Nagasaki 852-8521, Japan.
J Control Release. 2004 Sep 30;99(2):329-37. doi: 10.1016/j.jconrel.2004.07.012.
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.
我们之前表明，第六代树枝状聚（L-赖氨酸）（KG6）在体外具有高转染能力且无明显细胞毒性。在此，为了评估KG6作为一种在体内起作用的非病毒基因载体的潜力，我们研究了静脉注射后，与DOTAP/胆固醇脂质体和聚乙烯亚胺相比，用KG6递送的质粒DNA在小鼠体内的生物分布。Southern印迹分析显示，静脉注射后，C/A比为8.0的质粒DNA与KG6形成的复合物在血液中循环3小时。肝脏中的质粒DNA量逐渐减少。在荷瘤小鼠中，静脉注射后60分钟在肿瘤中观察到用KG6注射的质粒DNA，而使用DOTAP/胆固醇脂质体时肿瘤中不存在DNA。血液中与KG6形成的DNA复合物的隐身特性会在肿瘤中引起增强的渗透和滞留（EPR）效应。KG6有望成为一种有前景的候选物，能够在体内实现功能性基因递送。
