PH-sensitive And Redox-sensitive Fluorescent Probes And Their Application In The Imaging Of Tumor Cells

There are several physiological differences,such as extracellular pH and redox state,between the solid tumors and normal tissues.Many solid tumors contain hypoxic regions and lower extracellular pH.These differences can be exploited for selective cancer imaging and treatment.So we developed a pH-sensitive fluorescent probe and two redox-sensitive probes in order to provide new tools for the study and visualization of tumors.First of all,a pH-sensitive fluorescent probe based on 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene(BODIPY) dye was synthesized.The probe molecule was designed on the basis of the PET mechanism.It was demonstrated to be highly sensitive within the pH range of 4.0-6.0 with a pKa value of 5.05 and was highly photostable,which makes it a potential pH fluorescent probe.To the best of our knowledge,there are few pH fluorescent probes which can function in the pH range from 4.0 to 6.0.We found that it couldn't determine the difference in pH between tumor cells and normal cells.But it is still a very useful tool as a acidic pH-sensor. The new pH-sensor will find its applications in studying acidic organelles in living cells.Secondly,two redox-sensitive fluorescent probes were developed and were used for evaluating the intracellular redox status of living cells.These two probes were designed on the basis of the fluorophore-nitroxide mechanism.They were sensitive to reducing environment.The newly synthesized probes were used to evaluate antioxidant capability of antioxidants vitamin C(VC) and glutathione(GSH).They can also be used as a complement to the widely used dye 2',7'-dichlorodihydro -fluorescein(DCFH) to evaluate the total ROS level of living cells.In living cells,the nitroxide moiety of the probes is reduced to hydroxylamine quickly,and becomes highly fluorescent.We found the difference in redox state between tumor cells and normal cells by using these new probes.Their application for in vivo imaging is in progress.Thirdly,the pH-sensitive fluorescent probe is a ester.We found that it was a good substrate of trypsin and lipase.So it can be used as a fluorescent probe for these enzymes.It will be a useful tool for high-throughput screening of inhibitors of these enzymes.