Multivalent glycopolymer micelles for targeted and ROS-responsive diagnosis and therapy of metabolic dysfunction-associated steatohepatitis

The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis (MASH) drives advanced liver pathology, but clinical management is limited by invasive diagnostics and therapeutics with side effects. Here, we report a galactose-modified, reactive oxygen species (ROS)-responsive glycopolymer micelle ( OTP-Gal ) for MASH management. Loaded with the lipid-sensitive dye Nile red (NR), NR@OTP-Gal enables non-invasive, real-time fluorescence imaging of hepatic lipid accumulation and longitudinal tracking of steatosis during MASH progression. Loaded with the farnesoid X receptor agonist obeticholic acid (OCA), OCA@OTP-Gal improves OCA aqueous solubility and hepatocyte-specific delivery, while its ROS-responsive backbone enables drug release in damaged liver cells. In a diet-induced MASH mouse model, OCA@OTP-Gal outperforms free OCA, significantly reducing hepatic steatosis, oxidative stress, and serum transaminase levels. Therapeutic efficacy can also be quantified non-invasively using the NR@OTP-Gal imaging probe. This work establishes OTP-Gal as a versatile platform for precise diagnosis, targeted treatment, and therapeutic monitoring of MASH.