Visualization of peroxynitrite in cyclophosphamide-induced oxidative stress by an activatable probe

Oxidative stress is considered to be one of the main contributors of cyclophosphamide (CP)-induced toxicity, and the generation of free radicals will cause the interruption of multiple signal transduction pathways. Peroxynitrite (ONOO-) has strong oxidation and nitrification ability and is considered as an indirect indicator of oxidative stress. Therefore, it is necessary to design a fluorescent probe that can detect ONOO- and monitor CP-induced oxidative stress during chemotherapy. Herein, we synthesized a lipid droplet targeting fluorescent probe SX-1 based on triphenylamine-benzoindocyanine. When ONOO- is added to the probe SX-1, the C--C bond in the probe is broken, thereby releasing fluorescence. The good spectral response characteristics enable SX-1 to successfully track the fluctuations of ONOO- in living cells. Most importantly, we provided the first visual evidence that the level of ONOO- in HeLa cells was up-regulated under CP induction. All results indicated that SX-1 has great potential in detecting drug-induced ONOO-, and provided a new detection tool for a deeper understanding of drug-induced organism injury.