Quantum Dot-Based Non-invasive Monitoring of Sinusoidal Endothelial Scavenger Function in Steatohepatitis

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent urgent medical challenges. Current non-invasive assessments rely on serum indices or tissue stiffness, and none visualizes functional changes within the liver, hindering drug discovery and patient management. In this study, we developed a non-invasive technique using semiconductor quantum dots, as blood-borne foreign particle mimics, to evaluate the scavenger function of liver sinusoidal endothelial cells (LSECs) via near-infrared optical imaging. Progression from MASLD to MASH induced a significant decline in the scavenger capability of LSECs, resulting in a marked reduction of intrahepatic quantum dot retention. Mechanistically, we demonstrated that quantum dots are recognized and internalized by scavenger receptor class A (SR-A) on LSECs, and that SR-A-mediated uptake progressively diminishes with increasing MASH severity. Crucially, quantum dot retention levels significantly correlated with both the progression and regression of MASH pathology. These findings demonstrate that quantum dot-based optical evaluation of LSEC scavenger function offers a highly sensitive, non-invasive diagnostic platform for staging MASH and assessing therapeutic efficacy.