通过NIR化传感器对HSA再吸收进行现场映射,作为用于脏保护药物发现的实际表型分析
Yufan Fan1, Bei Zhao2, Ya Zhang3
1Department of Nephrology, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China; State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
一个新的近红外 (NIR) 传感器,NCBP,可以实时监测人血清白蛋白 (HSA) 细胞内在管中的细胞内在. 这种传感器有助于选新的脏保护剂,以对抗药物诱导的损伤.
科学领域:
- 生物医学工程 生物医学工程
- 分子成像学分子成像学
- 药物发现 药物发现 药物发现
背景情况:
- 人类血清白蛋白 (HSA) 的管再吸收受损是药物诱导损伤 (DIKI) 的早期指标.
- 实时监测HSA内细胞分裂对于评估功能和识别保护剂至关重要.
研究的目的:
- 开发一种新的近红外 (NIR) 化传感器,用于实时,现场的HSA再吸收的时空成像.
- 利用传感器平台进行查和识别有效的脏保护剂,以防止西斯普拉丁诱导的脏毒性 (CINT).
主要方法:
- 基于扭曲的分子内电荷转移 (TICT) 机制,利用华法林-HSA相互作用,设计了一种氨酸衍生的NIR传感器 (NCBP).
- 验证了NCBP对HSA的快速绑定,具有高度敏感性,稳定性和选择性.
- 应用NCBP用于细胞和脏组织中HSA再吸收的现场成像,以及查脏保护性化合物.
主要成果:
- NCBP在与HSA结合时显示出79倍的光增强,具有瞬间反应和高选择性.
- 通过NCBP,可以对活细胞和组织中的HSA再吸收进行时空成像.
- 在CINT模型中,诺比 (NOB) 和4',7-二甲氧化 (DIF) 被确定为有效的脏保护剂,改善功能并减少管道损伤.
结论:
- 开发了一种基于ICT的NIR传感器 (NCBP),用于对HSA再吸收进行强大的实时成像.
- 建立了一个表型平台,用于细胞HSA贩运的时空映射.
- 确定NOB和DIF作为减轻西斯产生的毒性有前途的化合物.
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