Tunable membrane penetration-directed signal amplification for electrochemical determination of matrix metalloproteinase-2 in cancer diagnosis

Abstract

Cancer is now a leading cause of human death worldwide and discovering an underlying cancer risk is essential to enhance the survival rates of the patients. Herein, we report a facile and sensitive electrochemical biosensing method for the determination of matrix metalloproteinase-2 (MMP-2), a potential indicator in most solid tumors. The core of the method is the use of a well-designed peptide probe with tunable membrane penetration activity. Specifically, the membrane penetration activity of the peptide probe is initially inhibited by a blocking domain through electrostatic interaction. Once the probe is selectively recognized and cleaved by MMP-2, its membrane penetration activity is switched on, leading to large amounts of methylene blue molecules being released from liposomes. As a result, remarkably amplified electrochemical responses are obtained for the determination of target MMP-2. Under optimized conditions, our method has displayed a good sensing performance, showing a wider linear range from 50 fg/mL to 10 ng/mL and a low limit of detection at 13.3 fg/mL. Moreover, the method has been successfully applied to MMP-2 determination in the mimic tumor microenvironment and serum samples and proved the feasibility of the selective identification of cancer patients. Therefore, our method may suggest a potential use in the determination of protease-specific tumor biomarkers for pan-cancer screening.