High contrast NIR excitation probe monitoring Cu2+ in the endoplasmic reticulum for synergistic cuproptosis and ferroptosis anticancer therapy

Currently, cuproptosis mainly focuses on the Cu2+ induced morphology of mitochondria (Mito), the observation of endoplasmic reticulum (ER)-related Cu2+ content in cuproptosis is relatively lacking. Herein, we develop a hydroxyflavone (HF) based NIR excited fluorescent probe, BHCO, for exhibiting specific recognition of Cu2+. BHCO can accurately locate in ER and detect Cu2+ content in cuproptosis process. The two-photon fluorescence nature of BHCO enables to track both ferroptosis and cuproptosis processes with high resolution. Furthermore, BHCO can upgrade reactive oxygen species (ROS) under 720 nm excitation, which facilitates ferroptosis occurrence. We firmly convince the nonlinear optical (NLO) small molecules could provide a valid tool for rapid tumors elimination through synergistic ferroptosis and cuproptosis.