Dual-Locked Near-Infrared Fluorescent Probe for Real-Time Imaging of Hydrogen Sulfide/Matrix Metallopeptidase-2 In Vivo

Hydrogen sulfide (H₂S) and matrix metallopeptidase 2 (MMP-2) are inextricably linked in the occurrence and development of diseases and the treatment of diseases. However, most of the activatable imaging probes currently developed are single-locked probes that do not simultaneously detect H₂S and MMP-2 levels at disease sites and severely hinder the real-time and accurate analysis of the dynamic relationship between the two interrelated biomarkers. Herein, we report a dual-locked H₂S/MMP-2-activatable near-infrared (NIR) fluorescent imaging probe through a dual-Förster resonance energy transfer (FRET) mechanism that specifically detects tumors or acute lung injury (ALI) and establishes the dynamic relationship between the H₂S level and MMP-2 expression. Initially, the fluorescence of the probe is turned off due to energy transfer from methylene blue (MB) to both the cationic electrochromic material (dicationic 1,1,4,4-tetraarylbutadiene, EM <b>1</b>²⁺) and quencher QSY21. Upon reaction with H₂S/MMP-2 in tumors or ALI, the NIR fluorescence of the probe is activated, enabling accurate real-time imaging of tumors or ALI. Additionally, this probe precisely tracks the effects of exogenous H₂S in tumors or glucocorticoids for the treatment of ALI on MMP-2 expression, providing a powerful molecular imaging tool for early prediction of treatment outcomes in tumors and ALI.