MMP-9-responsive probe for fluorescence-magnetic resonance dual-mode imaging of hepatocellular carcinoma models with different metastatic capacities

Autor: Wang, Qiuye, Sun, Yabing, Lai, Liangxue, Cui, Haijing, Ye, Yonglong, Yang, Ming, Zhu, Weihao, Yuan, Bo, Mao, Quanliang, Ren, Wenzhi, Wu, Aiguo
Zdroj: Chinese Chemical Letters; 20240101, Issue: Preprints
Abstrakt: Visual assessment of tumor metastatic capacity is crucial for predicting hepatocellular carcinoma (HCC) prognosis and guiding clinical therapeutic approaches. In this study, we developed an enzyme-responsive probe based on the peptide GK10, which is selectively cleaved by matrix metalloproteinase-9 (MMP-9), a critical marker for metastasis in HCC. The GK10 peptide was conjugated with near-infrared fluorescent molecule IR783, fluorescent quencher black hole quencher 3 (BHQ3), and magnetic resonance (MR) contrast agent DOTA-Gd, forming the IR783-GK10-BHQ3-Gd probe. Upon MMP-9 cleavage of GK10, BHQ3 is released from the probe, thereby amplifying the previously quenched IR783 fluorescence signal. In vitroexperiments demonstrate the probe's impressive detection limit for MMP-9, as low as 1.84 ng/mL. Moreover, in vivoimaging results reveal that the probe can differentiate liver cancers with varying metastatic capacities. The fluorescence and MR imaging signal intensity of high metastatic HCC are approximately 1.2 times greater than that of low metastatic HCC. Thus, this engineered probe holds promise as a valuable tool for evaluating HCC metastatic capacity through fluorescence-MR dual-mode imaging.
Databáze: Supplemental Index