NIR fluorescent probe with variable lipophilicity for imaging lysosomal copper during cuproptosis in HCC cells

Abstract

Copper is essential for the activity of vitally important enzymes, while it is toxicity when in excess. Recent research indicates that cells will undergo cuproptosis induced by copper-ionopheres, a kind of copper-dependent programmed death. Cuproptosis shows great potential in counteracting tumor resistance to traditional therapies. Lysosomes should be put more attention, as they are pivot of cellular copper regulation and trafficking. Herein, we developed a novel NIR fluorescent probe, CyCu, to describe lysosomal copper pools during cuproptosis. CyCu shows turn-on response and great selectivity to copper at the maximum emission wavelength of 730 nm. CyCu can accurately target to lysosomes and indicate lysosomal copper pools fluctuation during cuproptosis. The increase of fluorescence intensity of CyCu in glucose-lack HepG2 cells also shows cells preferable to respiration are more sensitive to copper and easier to suffer cuproptosis. So, lysosomal copper, imaged by CyCu, could be a new target of research of HCC (hepatocellular carcinoma) treatment.