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.