...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Gene Therapy and Molecular Biology >Surface-shielded polycation-based systems targetingreporter and therapeutic genes to distant tumors
【24h】

Surface-shielded polycation-based systems targetingreporter and therapeutic genes to distant tumors

机译：基于表面屏蔽聚阳离子的系统，将报告基因和治疗基因靶向远处的肿瘤

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We have developed surface-shielded transferrin-polyethylenimine (Tf-PEI) - based gene delivery systems which are able to target gene expression to distant tumors after systemic application in murine models. For systemic in vivo application the biophysical parameters of transfection complexes, such as particle size, stability, surface charge, and modification with targeting ligand, were found to be critical for DNA biodistribution, toxicity, and gene transfer efficacy. Two major mechanisms may contribute to the tumor-specific targeting: active targeting via receptor- mediated cell binding and passive targeting via shielding of the surface charge of the complexes. Shielding reduces plasma protein and erythrocyte binding, resulting in prolonged blood circulation and extravasation of DNA complexes in areas of vascular leakiness of the tumor tissue. Shielding of surface charges can be achieved by coating polycation/DNA complexes with either polyethylene glycol (PEG) or by incorporating Tf ligand at high densities. Systemic application of surface-shielded transferrin-polyethylenimine-based DNA complexes coding for tumor necrosis factor (TNFα) localized gene expression to distant tumors, resulting in pronounced hemorrhagic tumor necrosis and inhibition of tumor growth. TNFα activity was confined to the tumor without systemic TNF-related toxicity.
机译：我们已经开发了基于表面屏蔽的转铁蛋白-聚乙烯亚胺（Tf-PEI）的基因传递系统，该系统在小鼠模型中全身应用后能够将基因表达靶向远处的肿瘤。对于全身体内应用，发现转染复合物的生物物理参数，例如粒度，稳定性，表面电荷和靶向配体修饰，对于DNA生物分布，毒性和基因转移功效至关重要。肿瘤特异性靶向可能有两种主要机制：通过受体介导的细胞结合的主动靶向和通过屏蔽复合物的表面电荷的被动靶向。屏蔽减少了血浆蛋白和红细胞的结合，导致血液循环的延长和肿瘤组织血管渗漏区域中DNA复合物的外渗。表面电荷的屏蔽可通过用聚乙二醇（PEG）涂覆聚阳离子/ DNA复合物或以高密度掺入Tf配体来实现。全身应用编码肿瘤坏死因子（TNFα）的表面屏蔽的转铁蛋白-聚乙烯亚胺基DNA复合物定位基因表达到远处的肿瘤，导致明显的出血性肿瘤坏死并抑制肿瘤的生长。 TNFα活性仅限于肿瘤，无全身性TNF相关毒性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号