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自燃生物响应MR探针的分子工程

Jian-Hong Tang¹, Hao Li¹, Chaonan Yuan¹

¹Departments of Chemistry, Molecular Biosciences, Neurobiology and Physiology, and Radiology, Northwestern University, Evanston, Illinois 60208, United States.

Journal of the American Chemical Society

|April 28, 2023

概括

研究人员开发了用于磁共振成像的先进酶激活剂. 这些新型甲基酸盐剂可显著增强体内图像对比度,以实时检测整个动物的生物事件.

科学领域:

生物医学成像
分子成像
对比剂的开发

背景情况:

实时生物事件检测对于生物学和治疗理解至关重要.
磁共振 (MR) 影像提供高分辨率和深度透的非侵入性3D解剖视觉.
酶激活剂是基因表达报告和体内对比度增强的有价值工具.

研究的目的:

开发一种基于基酸盐的新型Gd (III) 复合物,以显著改善MR成像对比度.
创建一个自我燃烧,酶可激活的药物,
研究MR信号增强背后的分子机制.

主要方法:

开发一种新的基碳酸盐Gd (III) 复合物.
在"关闭状态"和酶处理后测量MR放松性.
使用单射线结晶学和核磁放松分散 (NMRD) 分析.
对生物反应剂的性能进行体内测试.

主要成果:

甲基酸盐剂具有较低的"关闭状态"MR放松性 (r1=1. 8mM-1s-1在1. 41T).
酶处理导致放松性显著增加 (Δr1 = 106%),与之前的药物相比显著改善 (Δr1 ~ 20%).
结构和动态分析为MR信号增强机制提供了分子层面的洞察力.

结论:

已经证明了一种基于基酸盐的新型自我燃烧分子平台,用于酶的生物反应性MR剂.
这种平台为实时生物事件检测提供了极大改进的体内图像对比度.
开发的平台可以适应各种目标,使刺激响应材料和多种生物医学应用成为可能.

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