Imaging lipid deposition induced by local hypoxia in degenerative aortic valve disease using a twisted intramolecular charge transfer (TICT)-based lipid droplet-targeting probe

A novel twisted intramolecular charge transfer (TICT)-based fluorescent probe, NMCTI, specifically engineered for selective visualization of lipid droplets (LDs) under hypoxic pathological conditions was developed. NMCTI exhibited an impressive Stokes shift of 112 nm, substantial solvatochromic fluorescence properties, and minimal cytotoxic effects. In cellular experiments, NMCTI demonstrated selective targeting and accumulation within LDs in HeLa cells, HUVECs and HL-1 mouse cardiomyocytes (HL-1 cells), accompanied by outstanding photostability, enabling clear and robust visualization of LDs under hypoxic conditions. Additionally, ex vivo imaging experiments on human valve tissues confirmed NMCTI's capability to clearly highlight lipid deposits in stenotic aortic valves. The imaging results were consistent with traditional histological staining, effectively differentiating pathological valves from healthy controls. These findings indicate that NMCTI can serve as a highly effective fluorescent imaging tool, significantly enhancing the detection and understanding of lipid accumulation in cardiovascular diseases, thereby contributing to improved diagnostic accuracy and therapeutic approaches for degenerative aortic valve disease (DAD).

Graphical Abstract