组织蛋白酶B响应的超极化129Xe MRI探针对肺癌细胞的超灵敏探测
收稿日期: 2020-04-25
网络出版日期: 2020-05-27
基金资助
国家自然科学基金资助项目(91859206);国家自然科学基金资助项目(81625011);国家重点研发计划(2016YFC1304704);中国科学院前沿科学重点研究计划(QYZDY-SSWSLH018)
Cathepsin B Triggered Hyperpolarization 129Xe MRI Probe for Ultra-Sensitive Lung Cancer Cells Detection
Received date: 2020-04-25
Online published: 2020-05-27
组织蛋白酶B（Cat B）是一种溶酶体半胱氨酸蛋白酶，在细胞代谢中起重要作用.已有研究表明Cat B在肺癌细胞中会过表达.因此，细胞内Cat B水平的检测非常重要.迄今为止，细胞内Cat B的检测方法主要为荧光成像，但该技术受限于渗透性和自发荧光背景干扰.为了解决这些问题，我们设计了一种基于超极化129Xe磁共振成像的新型探针.它由一个作为129Xe核磁共振（NMR）报告基团的穴番分子笼和一个作为Cat B特异性可裂解基团的酰胺键组成.当探针与Cat B相互作用时，酰胺键的断裂会导致其129Xe化学位移发生变化.结合超极化-化学交换饱和转移（Hyper-CEST）技术，可为Cat B提供一种新颖的检测方法.
关键词： 核磁共振(NMR); 造影剂; 肺癌; 超极化129Xe MRI探针; 组织蛋白酶B; 化学交换饱和转移(CEST)
王崇武 , 黄曦 , 石磊 , 陈世桢 , 周欣 . 组织蛋白酶B响应的超极化129Xe MRI探针对肺癌细胞的超灵敏探测[J]. 波谱学杂志, 2021 , 38(3) : 336 -344 . DOI: 10.11938/cjmr20202828
Cathepsin B (Cat B) is a lysosomal cysteine protease that plays an essential role in cellular metabolism. Cat B is overexpressed in lung cancer cells. Fluorescence imaging techniques have been developed for measuring intracellular Cat B levels, which, however, suffers from limited penetration depth and interferences from autofluorescence background. To resolve these technical difficulties, we designed a novel Cat B biosensor detected by hyperpolarized xenon magnetic resonance imaging. It consists of a cryptophane cage as a 129Xe NMR reporter and an amide bond as a Cat B-specific cleavable group. When the biosensor interacts with Cat B, the cleavage of amide bond leads to changes in 129Xe chemical shift. Combing with hyperpolarization-chemical exchange saturation transfer (Hyper-CEST), our biosensor provides a novel method for responsive detection of Cat B.
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