ATP-responsive NIR-Ⅱ fluorescence/mass spectrometry dual-modal nanoprobe for precision diagnosis of metabolic dysfunction-associated steatohepatitis.

BACKGROUND

Metabolic dysfunction-associated steatohepatitis (MASH) requires analytical tools capable of noninvasive and dynamic evaluation of hepatic metabolic dysfunction in vivo. Adenosine triphosphate (ATP) is a key indicator of mitochondrial activity and energy metabolism, yet its selective detection in complex biological environments remains challenging.

RESULTS

An ATP-responsive dual-modal nanoplatform, NA1060@ZIF-90, was developed by integrating near-infrared Ⅱ (NIR-Ⅱ) fluorescence imaging with mass spectrometry imaging (MSI). ATP-Zn2+ coordination induces disassembly of the ZIF-90 framework, activating a turn-on NIR-Ⅱ fluorescence signal and enabling sensitive and selective ATP detection. The platform allows real-time visualization of hepatic ATP depletion and recovery in free-fatty-acid (FFA) treated hepatocytes and a methionine-choline-deficient (MCD) diet-induced MASH mouse model. MSI analysis further provides spatial molecular validation by correlating probe activation with lipid metabolic remodeling.

SIGNIFICANCE: This work presents an analytical strategy that couples dynamic in vivo metabolic imaging with label-free spatial molecular analysis, offering a robust framework for MASH diagnosis, disease evaluation, and therapeutic efficacy assessment, and highlighting the potential of ATP-responsive nanomaterials in metabolic disease analysis.