A benzothiazole-based fluorescence probe for imaging of peroxynitrite during ferroptosis and diagnosis of tumor tissues

Ferroptosis, as a new regulated mode of cell death, is mainly characterized by iron-dependent accumulation of lipid peroxides related to reactive oxygen species (ROS). However, the changes of peroxynitrite (ONOO−) during ferroptosis are not very clear due to the limited reports. On the other hand, ONOO− has become an endogenous toxicant leading to cell apoptosis and necrosis. Thus, it is urgent to develop molecular tools with high selectivity and sensitivity to monitor intracellular ONOO−. Herein, we presented a fluorescent probe, BTMO-PN, by introducing a phenylboronic acid ester as the ONOO− recognition site into benzothiazolyl derivative. BTMO-PN exhibited a rapid and marked fluorescence enhancement signal toward ONOO−, owing to the ONOO−-triggered the cleavage of phenylboronic acid ester to release strongly fluorescent BTMO. Moreover, BTMO-PN could image endogenous and exogenous ONOO− changes in live cells. Importantly, using BTMO-PN, we demonstrated the up-generation of ONOO− levels in cancer cells during ferroptosis. Furthermore, BTMO-PN has successfully been applied for distinguishing tumor tissues from normal tissues with excellent contrast, making it great potential for cancer diagnosis by detecting the ONOO− changes.Graphical abstract