H₂O₂ accumulation promoting internalization of ox-LDL in early atherosclerosis revealed <i>via</i> a synergistic dual-functional NIR fluorescence probe

The equilibrium of lipid metabolism is critical to sustaining human health. Metabolic disorders often result in a variety of cardiovascular illnesses, especially atherosclerosis. Atherosclerosis is characterized by complicated complications and high mortality. Cholesterol deposition and oxidative stress have been considered as critical mechanisms in the occurrence and progression of atherosclerosis, however, the relationship between oxidative stress and lipid accumulation remains a puzzle in foam cells during the early stages of atherosclerosis development. Hydrogen peroxide (H₂O₂) has been reported to participate in various signaling pathways associated with atherosclerotic diseases. Additionally, the excessive intake of oxidized low-density lipoprotein (ox-LDL) leads to cholesterol accumulation and viscosity increasing in foam cells. Therefore, it is critical to investigate the internalization and modification of ox-LDL by H₂O₂ in foam cells. Herein, we developed a near-infrared, synergistic dual-functional fluorescent probe capable of detecting H₂O₂ and viscosity simultaneously with high selectivity and sensitivity. Through <i>in situ</i> imaging of H₂O₂ and viscosity <i>in vivo</i>, we discovered that H₂O₂ accumulation leads to an increased intake of ox-LDL in the early stages of plaque formation. This finding establishes a new experimental approach and theoretical foundation for the diagnosis and treatment of atherosclerosis, as well as the development of new medications.