A Dual-Responsive NIR Fluorescent Probe for Diagnosis and Therapeutic Evaluation of Alcoholic Liver Disease and Drug-Induced Liver Disease

Abstract

Acute liver injury (ALI), including alcoholic liver disease (ALD) and drug-induced liver injury (DILI), poses significant diagnostic and therapeutic challenges because of the absence of specific biomarkers that distinguish it from other pathologies (e.g., acute lung or skeletal muscle injuries). Here, we report the synthesis of a probe, TXET, which exhibits dual responsiveness to viscosity and sulfur dioxide (SO₂) derivatives. The probe’s carbon-carbon double bond undergoes a Michael addition reaction with bisulfite ion (HSO₃⁻), blocking the photoinduced electron transfer (PET) process and enabling “off-on” detection of SO₂ derivatives. Concurrently, as viscosity increases, rotation of the carbon-carbon bond in TXET is restricted, leading to the emission of intense red fluorescence. In vivo studies demonstrated that TXET can monitor dynamic changes in SO₂ concentration and viscosity in ALD and DILI mice. Furthermore, TXET facilitated a comparative assessment of four drugs used in ALI treatment, revealing distinct therapeutic effects of these drugs in ALD and DILI models. This work highlights that TXET serves as a promising tool for the diagnosis of ALI and evaluation of therapeutic efficacy.