Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma.
Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma.
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三种聚乙烯亚胺衍生纳米颗粒作为肾细胞癌基因治疗递送系统的比较
DOI：
10.1186/1479-5876-9-46
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发表时间：
2011-04-23
影响因子：
7.4
通讯作者：
Liang S
中科院分区：
文献类型：
--
作者：
Xu Z;Shen G;Xia X;Zhao X;Zhang P;Wu H;Guo Q;Qian Z;Wei Y;Liang S
背景聚乙烯亚胺（Polyethyleneimine，PEI）能与带负电荷的DNA通过静电作用形成纳米复合物，被广泛应用于基因传递系统。但PEI本身存在一些缺陷，不适合基因表达的维持。因此，针对PEI的性质进行了一些修饰，以提高其在基因递送中的应用价值。在这项研究中，三种改性PEI衍生物，包括聚（ε-己内酯）-pluronic-poly（ε-己内酯）接枝PEI方法采用MTT法和GFP标记基因（编码绿色荧光蛋白），对PCFC-g-PEI、叶酸-PCFC-异佛尔酮二异氰酸酯-PEI（FA-PEAs）和肝素-PEI（HPEI）的体外细胞毒性和体内转染效率进行了研究。体外细胞毒性和转染活性测定。以OS-RC-2细胞接种BALB/c裸鼠，建立肾细胞癌（RCC）模型，检测三种PEI纳米粒作为基因载体的基因治疗效果。用半定量RT-PCR和免疫组化方法分析靶基因Von Hippel-Lindau（VHL）在治疗后肿瘤组织中的表达情况。结果与分子量为25 kD或2 kD的前体PEI相比，三种修饰的PEI衍生生物材料的转染效率提高，细胞毒性降低。用FA-PEAs转染VHL质粒治疗小鼠肾细胞癌模型，平均肿瘤体积明显缩小30%。VHL处理组VHL基因表达明显增强。结论PCFC-g-PEI、FA-PEAs和HPEI经修饰后，其体外转染效率明显提高，毒性明显降低。FA-PEAs可能为将来治疗肾细胞癌甚至其他癌症提供一种潜在的基因递送系统。
BackgroundPolyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene delivery system. However, PEI has some defects that are not fit for keeping on gene expression. Therefore, some modifications against PEI properties have been done to improve their application value in gene delivery. In this study, three modified PEI derivatives, including poly(ε-caprolactone)-pluronic-poly(ε-caprolactone) grafted PEI (PCFC-g-PEI), folic acid-PCFC-isophorone diidocyanate-PEI (FA-PEAs) and heparin-PEI (HPEI), were evaluated in terms of their cytotoxicity and transfection efficiencyin vitroandin vivoin order to ascertain their potential application in gene therapy.MethodsMTT assay and a marker GFP gene, encoding green fluorescent protein, were used to evaluate cell toxicity and transfection activity of the three modified PEIin vitro. Renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells to detect the gene therapy effects using the three PEI-derived nanoparticles as gene delivery vehicles. The expression status of a target gene Von Hippel-Lindau (VHL) in treated tumor tissues was analyzed by semiquantitative RT-PCR and immunohistochemistry.ResultsEach of three modified PEI-derived biomaterials had an increased transfection efficiency and a lower cytotoxicity compared with its precursor PEI with 25-kD or 2-kD molecule weightin vitro. And the mean tumor volume was obviously decreased 30% by using FA-PEAs to transfer VHL plasmids to treat mice RCC models. The VHL gene expression was greatly improved in the VHL-treated group. While there was no obvious tumor inhibition treated by PCFC-g-PEI:VHL and HPEI:VHL complexes.ConclusionsThe three modified PEI-derived biomaterials, including PCFC-g-PEI, FA-PEAs and HPEI, had an increased transfection efficiencyin vitroand obviously lower toxicities compared with their precursor PEI molecules. The FA-PEAs probably provide a potential gene delivery system to treat RCC even other cancers in future.
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影响因子：
14
作者：
Corsi, K;Chellat, F;Fernandes, JC
通讯作者：
Fernandes, JC
影响因子：
4.7
作者：
Furgeson, DY;Chan, WS;Kim, SW
通讯作者：
Kim, SW
影响因子：
5.1
作者：
Aoki, K;Furuhata, S;Yoshida, T
通讯作者：
Yoshida, T
影响因子：
14.9
作者：
Kreiss, P;Cameron, B;Pitard, B
通讯作者：
Pitard, B
影响因子：
12.4
作者：
Furgeson, DY;Yockman, JW;Kim, SW
通讯作者：
Kim, SW