Lanthanide complex-based dual-modal probes for background-free time-gated luminescence and 19F magnetic resonance detection of hypochlorous acid in acute kidney injury

Abstract

Acute kidney injury (AKI) is a life-threatening clinical syndrome often triggered by drug-induced nephrotoxicity, yet its early diagnosis remains challenging due to the lack of sensitive and specific biomarkers. Hypochlorous acid (HClO), a highly reactive oxygen species, plays a pivotal role in the oxidative damage that drives AKI progression. To achieve precise in situ monitoring of this pathological event, we designed and synthesized a water-soluble lanthanide complex probe, Ln(SDHH)₃(DPBT) (Ln³⁺ = Eu³⁺, Gd³⁺), as a dual-modal sensing platform for intrinsically background-free detection of HClO via time-gated luminescence (TGL) and ¹⁹F magnetic resonance (MR) sensing. By integrating a sulfonate-functionalized β-diketonate ligand (SDHH) to enhanced aqueous solubility and biocompatibility, together with an extended π-conjugated antenna (DPBT) to enable visible-light excitation, this probe overcomes the limitations of traditional lanthanide complex-based probes. Upon exposure to HClO, selective oxidative cleavage of the SDHH ligand induces rapid quenching of Eu³⁺ luminescence and simultaneously restores the ¹⁹F MR signal by eliminating the Gd³⁺-mediated paramagnetic relaxation enhancement (PRE) effect. The probe exhibits an ultrafast response (< 7 s), high selectivity and sensitivity (LOD = 87 nM for TGL detection), and exceptional biocompatibility. Leveraging these advantages, Eu(SDHH)₃(DPBT) successfully enabled high-contrast visualization of endogenous HClO fluctuations in cisplatin-stimulated renal cells and in an AKI mouse model. Collectively, this dual-modal platform provides a robust tool for real-time in situ visualization of HClO, facilitating mechanistic investigations and early diagnosis of oxidative stress–related organ Injury.