This investigation aims to determine experimentally whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of NK4 plasmid DNA and suppressing tumor growth. NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as an HGF-antagonist and angiogenesis inhibitor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow for polyionic complexation with NK4 plasmid DNA. The cationized dextran was additionally modified with poly(ethylene glycol) (PEG) molecules giving PEG engrafted cationized dextran. Significant suppression of tumor growth was observed when PEG engrafted cationized dextran-NK4 plasmid DNA complexes were intravenously injected into mice carrying a subcutaneous Lewis lung carcinoma tumor mass with subsequent US irradiation when compared with the cationized dextran-NK4 plasmid DNA complex and naked NK4 plasmid DNA with or without US irradiation. We conclude that complexation with PEG-engrafted cationized dextran in combination with US irradiation is a promising way to target the NK4 plasmid DNA to the tumor for gene expression.

中文翻译：

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使用结合了NK4质粒DNA-PEG的阳离子化葡聚糖复合物和超声辐射的组合，可以增强对肿瘤生长的抑制作用。

这项研究旨在通过实验确定超声（US）辐射是否有效增强NK4质粒DNA的体内基因表达并抑制肿瘤生长。NK4由NH2末端发夹和随后的肝细胞生长因子（HGF）的四环结构域组成，可作为HGF拮抗剂和血管生成抑制剂。通过将精胺引入羟基使葡聚糖阳离子化，以使其与NK4质粒DNA发生离子复合。将阳离子化的葡聚糖另外用聚（乙二醇）（PEG）分子修饰，得到PEG接枝的阳离子化的葡聚糖。与阳离子化的右旋糖酐-NK4质粒DNA复合物和裸露的NK4质粒DNA相比，将PEG植入的阳离子化的右旋糖酐-NK4质粒DNA复合物静脉内注射到携带皮下Lewis肺癌肿瘤块并随后进行US照射的小鼠中，观察到肿瘤生长的显着抑制有无美国辐射。我们得出的结论是，与PEG植入的阳离子化右旋糖酐结合US辐射进行复合是将NK4质粒DNA靶向肿瘤进行基因表达的有前途的方法。