In vivo gene delivery by cationic tetraamino fullerene
In vivo gene delivery by cationic tetraamino fullerene
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DOI：
10.1073/pnas.0909223107
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发表时间：
2010-03-23
影响因子：
11.1
通讯作者：
Nakamura, Eiichi
中科院分区：
文献类型：
--
作者：
Maeda-Mamiya, Rui;Noiri, Eisei;Nakamura, Eiichi
纳米技术在医学生物学中的应用取得了显著的成功。水溶性富勒烯具有独特的两亲性，通过化学修饰可以形成自组装结构，是一种极具生物应用潜力的分子。四（哌嗪基）富勒烯环氧化物（TPFE）在体外的有效基因传递和其优越性，脂质体已在以前的报告。在这项研究中，我们评估了TPFE体内基因递送的功效。与Lipofectin相比，TPFE对妊娠雌性ICR小鼠的增强型绿色荧光蛋白基因（EGFP）的递送表现出明显的器官选择性;此外，TPFE在肝脏和脾脏中发现了更高的基因表达，但在肺中没有发现。TPFE对肝脏和肾脏无急性毒性，但Lipofectin可显著增加肝酶和血尿素氮。在胎儿组织中，TPFE和Lipofectin均不诱导EGFP基因表达。将胰岛素2基因递送至雌性C57/BL 6小鼠增加血浆胰岛素水平并降低血糖浓度，表明基于TPFE的基因递送用于临床应用的潜力。总之，这项研究首次证明了使用水溶性富勒烯的有效体内基因递送。
Application of nanotechnology to medical biology has brought remarkable success. Water-soluble fullerenes are molecules with great potential for biological use because they can endow unique characteristics of amphipathic property and form a self-assembled structure by chemical modification. Effective gene delivery in vitro with tetra(piperazino) fullerene epoxide (TPFE) and its superiority to Lipofectin have been described in a previous report. For this study, we evaluated the efficacy of in vivo gene delivery by TPFE. Delivery of enhanced green fluorescent protein gene (EGFP) by TPFE on pregnant female ICR mice showed distinct organ selectivity compared with Lipofectin; moreover, higher gene expression by TPFE was found in liver and spleen, but not in the lung. No acute toxicity of TPFE was found for the liver and kidney, although Lipofectin significantly increased liver enzymes and blood urea nitrogen. In fetal tissues, neither TPFE nor Lipofectin induced EGFP gene expression. Delivery of insulin 2 gene to female C57/BL6 mice increased plasma insulin levels and reduced blood glucose concentrations, indicating the potential of TPFE-based gene delivery for clinical application. In conclusion, this study demonstrated effective gene delivery in vivo for the first time using a water-soluble fullerene.