组织蛋白酶B响应的超极化^(129)Xe MRI探针对肺癌细胞的超灵敏探测

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

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^(129)Xe磁共振成像的新型探针.它由一个作为^(129)Xe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^(129)Xe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.

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^(129)Xe 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^(129)Xe chemical shift.Combing with hyperpolarization-chemical exchange saturation transfer(Hyper-CEST),our biosensor provides a novel method for responsive detection of Cat B.