Magnesium-Chelating Vitamin C Nanostructures Induce p38 MAPK Vitcylation for Hepatic Fibrosis Therapy

Vitamin C is essential for physiological health, yet its potential biological effects are limited by the difficulty of maintaining locally high concentrations under oxidative conditions. Here we developed a redox-stable magnesium-vitamin C coordination self-assembly encapsulated in a biomimetic liposomal shell. This nanostructure accumulates in the liver and protects vitamin C from degradation caused by Reactive Oxygen Species. The localized enrichment enables covalent vitcylation of p38 MAPK at K53 and K54, which blocks its nucleus translocation and triggers G2/M cell-cycle arrest, thereby limiting profibrotic cell proliferation. We identify this modification as a vitamin C-derived post-translational modification that directly regulates MAPK signaling in hepatic stellate cells. This mechanism distinguishes VC from conventional antioxidant paradigms and reveals its capacity to act as a covalent modulator of signaling pathways. More broadly, our findings establish vitcylation as a biochemical principle linking nutrient chemistry to cell cycle control and offer therapeutic potential for liver fibrosis.

hepatic fibrosis; hepatic stellate cells; molecules self-assembly; post-translational modification; vitcylation.