mitochondrial-targeting near-infraredfluorescent probe for bioimaging and evaluating endogenous superoxide anionchanges during ischemia/reperfusion injury

XiaoyueHan【韩潇玥】,^ad Rui Wang【王蕊】,^aXinyu Song【宋新宇】,^bc Fabiao Yu【于法标】,*^ac Changjun Lv【吕长俊】^bc and Lingxin Chen【陈令新】*^ac

^aKeyLaboratory of Coastal Environmental Processes and Ecological Remediation;Research Centre for Coastal Environmental Engineering and Technology, YantaiInstitute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003,China.

^b Department of Respiratory Medicine, BinzhouMedical University Hospital, Binzhou 256603, China.

^c Medicine Research Center, Institute ofMolecular Medicine, Binzhou Medical University, Yantai 264003, China.

^d University of Chinese Academy of Sciences,Beijing 100049, China.

*Correspondingauthor: fbyu@yic.ac.cn; lxchen@yic.ac.cn

Abstract: The outburst of superoxideanion (O₂^•−) in mitochondrial during ischemia/reperfusion(I/R) process will cause a series of oxidative damage including polarity lossof mitochondrial membrane potential, overload of secondary cellular calcium,and cascade apoptosis. To monitor the O₂^•− level fluctuationsas well as to evaluate the relationship between O₂^•− concentrationand the degree of cell apoptosis during I/R process, we propose a ratiometricnear-infrared mitochondrial targeting fluorescent probe Mito-Cy-Tfs for the detection of level changes of O₂^•−in cells and in vivo. The probeMito-Cy-Tfs is composed of threemoieties: near-infrared heptamethine cyanine asfluorescence signal transducer, trifluoromethanesulfonamideas fluorescence modulator, and lipophilic triphenylphosphonium cation asmitochondrial guider. The probe can well locate in mitochondria and respond theconcentration changes of endogenous O₂^•− selectively andsensitively. The probe has been successfully utilized to image the endogenous O₂^•−fluctuations in four kinds of cell I/R models(glucosedeprivation/reperfusion, serum deprivation/reperfusion, oxygendeprivation/reperfusion and glucose-serum-oxygen deprivation/reperfusion). Theprobe also exhibits deep tissue penetration for real-time imaging of O₂^•−concentrationin liver of I/R mice model. We confirm that the adoption of ischemic preconditioning(IPC) and postconditioning (IPTC) can protect liver from I/R injury. The probecan be employed to accurately indicate and evaluate the mutual relationshipbetween the levels of O₂^•− and the degrees of organdamage during I/R, IPC and IPTC processes. The above applications make our newprobe a potential candidate for the clinical surgery assessment.

Keywords:near-infrared fluorescent probes, ratiometric bioimaging,superoxideanion, mitochondrial localization, ischemia/reperfusioninjury

http://www.sciencedirect.com/science/article/pii/S0142961217307688#MMCvFirst