H2O2 Accumulation Promoting Internalization of ox-LDL in Early Atherosclerosis Revealed via 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 in-situ imaging of H2O2 and viscosity in vivo, we discovered that H2O2 accumulation leads to 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.