...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Real-time analysis of uptake and bioactivatable cleavage of luciferin-transporter conjugates in transgenic reporter mice
【24h】

Real-time analysis of uptake and bioactivatable cleavage of luciferin-transporter conjugates in transgenic reporter mice

机译：实时分析转基因报告小鼠中萤光素-转运蛋白结合物的摄取和生物活化裂解

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Many therapeutic leads fail to advance clinically because of bio-availability, selectivity, and formulation problems. Molecular transporters can be used to address these problems. Molecular transporter conjugates of otherwise poorly soluble or poorly bioavailable drugs or probes exhibit excellent solubility in water and biological fluids and at the same time an enhanced ability to enter tissues and cells and with modification to do so selectively. For many conjugates, however, it is necessary to release the drug/probe cargo from the transporter after uptake to achieve activity. Here, we describe an imaging method that provides quantification of transporter conjugate uptake and cargo release in real-time in animal models. This method uses transgenic (luciferase) reporter mice and whole-body imaging, allowing noninva-sive quantification of transporter conjugate uptake and probe (luciferin) release in real time. This process effectively emulates drug-conjugate delivery, drug release, and drug turnover by an intracellular target, providing a facile method to evaluate comparative uptake of new transporters and efficacy and selectivity of linker release as required for fundamental studies and therapeutic applications.
机译：由于生物利用度，选择性和制剂问题，许多治疗方法无法在临床上取得进展。分子转运蛋白可用于解决这些问题。否则难溶或生物利用度差的药物或探针的分子转运蛋白偶联物在水和生物流体中显示出极好的溶解性，同时增强了进入组织和细胞的能力，并且经过修饰可以选择性地这样做。然而，对于许多缀合物，必须在摄取后从转运蛋白中释放药物/探针货物以实现活性。在这里，我们描述了一种成像方法，该方法可在动物模型中实时量化转运蛋白结合物的摄取和货物的释放。该方法使用转基因（荧光素酶）报告基因小鼠和全身成像，可实时定量转运蛋白结合物摄取和探针（荧光素）释放的无损定量。该过程有效地模拟了细胞内靶点的药物偶联物的递送，药物释放和药物周转，从而提供了一种简便的方法来评估新转运蛋白的相对摄取以及基础研究和治疗应用所需的接头释放的功效和选择性。

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