Constructing turn-on bioluminescent probes for real-time imaging of reactive oxygen species during cisplatin chemotherapy.

ABSTRACT

Real-time imaging of reactive oxygen species (ROS) during cisplatin chemotherapy of cancer is imperative to fully reveal their functions in the biological response to cisplatin. Currently, using a bioluminescent probe for real-time imaging of a specific ROS in vivo during cisplatin chemotherapy has not been achieved. Herein, three bioluminescent probes, F Probe, N Probe and P Probe were synthesized for real-time imaging of the primary ROS, O2•-. They all consisted of a bioluminescent emitter D-luciferin (D-LH2) and an O2•--recognition group, and their bioluminescent signal could be turned on in response to O2•-. In vitro results indicated that P Probe was the most suitable one among the three probes for detection of O2•-, with high sensitivity, excellent selectivity and stability. P Probe was then successfully applied for real-time imaging of O2•- in both cancer cells and tumors during cisplatin chemotherapy. The imaging results demonstrated that O2•- amount in cancer cells increased with the increasing dose of cisplatin, and that cisplatin-induced upregulation of O2•- level in cancer cells was upstream of the cancer-killing pathway of cisplatin. We envision that P Probe may serve as an elucidative tool to further explore the role of O2•- in cisplatin chemotherapy.