Tumor targeting of gene expression through metal-coordinated conjugation with dextran (Retracted article. See vol. 232, pg. 266, 2016)
Tumor targeting of gene expression through metal-coordinated conjugation with dextran (Retracted article. See vol. 232, pg. 266, 2016)
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DOI：
10.1016/s0168-3659(02)00425-x
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发表时间：
2003-03-07
影响因子：
10.8
通讯作者：
Tabata, Y
中科院分区：
文献类型：
--
作者：
Hosseinkhani, H;Aoyama, T;Tabata, Y
通过葡聚糖衍生物与基于金属配位的螯合残基的缀合实现质粒DNA的肿瘤靶向。以二乙烯三胺五乙酸（DTPA）、亚精胺（Sd）和精胺（Sm）为原料，通过化学方法将其引入到葡聚糖的羟基上，得到葡聚糖-DTPA、葡聚糖-Sd和葡聚糖-Sm衍生物。通过Zn 2+配位的葡聚糖衍生物的缀合降低了质粒DNA的表观大小，这取决于衍生物类型。Zn ~（2+）与葡聚糖-Sm偶联后，质粒DNA的负zeta电位几乎为0 mV。当葡聚糖衍生物-质粒DNA缀合物与Zn ~（2+）的协调静脉注射到小鼠皮下携带Meth-AR-1纤维肉瘤时，葡聚糖-Sm-质粒DNA缀合物显着增强肿瘤中的基因表达水平，与其他葡聚糖衍生物和游离质粒DNA的缀合物相反。由Zn 2 +-协调的葡聚糖-Sm-质粒DNA缀合物产生的增强的基因表达对肿瘤是特异性的，而葡聚糖-Sm和质粒DNA的简单混合物是无效的。基因表达水平取决于引入的螯合残基的百分比、用于缀合物制备的质粒DNA/Sm残基的混合重量比和质粒DNA剂量。荧光显微镜研究显示，只有在注射具有Zn 2+配位的葡聚糖-Sm-质粒DNA缀合物后，才观察到质粒DNA在肿瘤组织中的定位。此外，偶联物诱导的基因表达在注射后持续超过10天。我们的结论是，Zn 2 +-协调的葡聚糖-Sm共轭是一种有前途的方式，使质粒DNA靶向肿瘤的基因表达，以及延长基因表达的持续时间。(C)2002 Elsevier Science B. V.保留所有权利。
Tumor targeting of plasmid DNA was achieved through the conjugation of dextran derivatives with chelate residues based on metal coordination. Diethylenetriamine pentaacetic acid (DTPA), spermidine (Sd), and spermine (Sm) were chemically introduced to the hydroxyl groups of dextran to obtain dextran-DTPA, dextran-Sd and dextran-Sm derivatives. Conjugation of the dextran derivative by Zn2+ coordination decreased the apparent size of the plasmid DNA, depending on the derivative type. The negative zeta potential of plasmid DNA became almost 0 mV after Zn2+-coordinated conjugation with dextran-Sm. When the dextran derivative-plasmid DNA conjugates with Zn2+ coordination were intravenously injected subcutaneously into mice bearing Meth-AR-1 fibrosarcoma, the dextran-Sm-plasmid DNA conjugate significantly enhanced the level of gene expression in the tumor, in contrast to the conjugate of other dextran derivatives and free plasmid DNA. The enhanced gene expression produced by the Zn2+-coordinated dextran-Sm-plasmid DNA conjugate was specific to the tumor, whereas a simple mixture of dextran-Sm and plasmid DNA was not effective. The level of gene expression depended on the percentage of chelate residues introduced, the mixing weight ratio of the plasmid DNA/Sm residue used for conjugate preparation, and the plasmid DNA dose. A fluorescent microscopic study revealed that localization of plasmid DNA in the tumor tissue was observed only after injection of the dextran-Sm-plasmid DNA conjugate with Zn2+ coordination. In addition, the gene expression induced by the conjugate lasted for more than 10 days after the injection. We conclude that Zn2+-coordinated dextran-Sm conjugation is a promising way to enable plasmid DNA to target the tumor in gene expression as well as to prolong the duration of gene expression. (C) 2002 Elsevier Science B.V. All rights reserved.