Long circulation of intravenously administered plasmid DNA delivered with dendritic poly(L-lysine) in the blood flow
Long circulation of intravenously administered plasmid DNA delivered with dendritic poly(L-lysine) in the blood flow
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DOI：
10.1016/j.jconrel.2004.07.012
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发表时间：
2004-09-30
影响因子：
10.8
通讯作者：
Niidome, T
中科院分区：
文献类型：
--
作者：
Kawano, T;Okuda, T;Niidome, T
我们以前的研究表明，第6代树枝状聚赖氨酸（KG 6）具有高的转染能力，在体外没有显着的细胞毒性。在这里，为了评估KG 6作为体内工作的非病毒基因载体的潜力，我们研究了静脉给药后与KG 6一起递送的质粒DNA在小鼠中的生物分布，与DOTAP/Chol脂质体和PEI进行比较。Southern印迹分析表明，质粒DNA与KG 6以8.0的C/A比复合物在静脉注射后在血液中循环31 t。肝脏中质粒DNA的量逐渐减少。在荷瘤小鼠中，在静脉注射后60分钟，在肿瘤中观察到注射了KG 6的质粒DNA，而使用DOTAP/Chol脂质体的肿瘤中不存在DNA。KG 6与DNA复合物在血液中的隐形特性将导致肿瘤中增强的渗透性和保留（EPR）效应。KG 6有望成为一个有前途的候选人，使功能性基因在体内输送。(C)2004 Elsevier B. V.保留所有权利。
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 It 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. (C) 2004 Elsevier B.V. All rights reserved.