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

doi:10.11938/cjmr20202828

摘要/Abstract

摘要：

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)

Abstract:

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.

Key words: nuclear magnetic resonance (NMR), contrast agents, lung cancer, hyperpolarization ¹²⁹Xe MRI probe, cathepsin B, chemical exchange saturation transfer (CEST)

中图分类号:

O482.53

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.

Chong-wu WANG,Xi HUANG,Lei SHI,Shi-zhen CHEN,Xin ZHOU. Cathepsin B Triggered Hyperpolarization ¹²⁹Xe MRI Probe for Ultra-Sensitive Lung Cancer Cells Detection[J]. Chinese Journal of Magnetic Resonance, 2021, 38(3): 336-344.

图/表 9

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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

Cathepsin B Triggered Hyperpolarization ¹²⁹Xe MRI Probe for Ultra-Sensitive Lung Cancer Cells Detection

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