Lanthanide complex-based probes for time-gated luminescence and 19F magnetic resonance imaging of hypochlorous acid in the liver.

Hypochlorous acid (HClO) is a highly reactive, short-lived oxidant in vivo whose fluctuating levels are closely linked to oxidative stress, inflammation, and tissue injury. However, its transient nature, low abundance, and interference from complex biological environments make precise detection as a biomarker of inflammatory diseases challenging. Here, we report a liver-targeted lanthanide complex probe, Ln(HAPP)3(DPBT) (Ln3+ = Eu3+, Gd3+), that functions as a dual-modal imaging probe for intrinsically background-free detection of HClO using time-gated luminescence (TGL) and 19F magnetic resonance imaging (MRI). The probe responds to HClO through oxidative cleavage of the β-diketonate ligand, resulting in rapid quenching of Eu3+ luminescence and simultaneous restoration of the 19F MR signal by abolishing the Gd3+-mediated paramagnetic relaxation enhancement (PRE) effect. Furthermore, incorporation of a galactose moiety enables asialoglycoprotein receptor (ASGPR)-mediated liver targeting, while the dipyrazolotriazine (DPBT) antenna effectively red-shifts the excitation wavelength into the visible region. The probe exhibits an ultrafast response (< 7 s), high sensitivity (LOD = 78 nM for TGL detection), excellent selectivity, and minimal cytotoxicity, allowing dynamic imaging of both exogenous and endogenous HClO in HepG2 cells and high-contrast visualization of HClO fluctuations in a mouse model of acetaminophen-induced liver injury. Collectively, this dual-modal platform provides a robust tool for real-time visualization of hepatic HClO, facilitating mechanistic investigations and early diagnosis of oxidative stress-related liver diseases.