The Design And Synthesis Of 3-hydroxyflavons Zn²⁺ Fluorescent Probe And Its Application In The Recognition Of Prostate Cancer Cells

Prostate cancer is a common malignant tumor in men and the second leading cause of cancer death in men except for lung cancer.The current clinical diagnosis is prostate-specific antigen,which is associated with considerable shortcomings in terms of specificity and sensitivity.The free Zn2+ as a candidate marker for prostate cancer has been studied for half a century.In the process of carcinogenesis,the concentration of Zn2+ in prostate cells decreased obviously because of the deficiency of zinc transporter.Therefore,the development of high affinity free Zn2 probes is helpful for new diagnostic reagents of prostate cancer.Although,a large number of Zn2+ fluorescent probes have been reported,fluorescent dyes with lower fluorescence background,higher sensitivity and selectivity,better cell-permeable properties and longer mean cell retention time are still in high demand.In our study,we reported the synthesis and pHotopHysical evaluation of zinc sensor 3HC-DPA,containing 3-hydroxychromone(3HC)as chromopHore moiety and a zinc-selective metal chelator moiety DPA.By UV titration,JOB curve test and crystal structure analysis,the 3HC-DPA and Zn2+ are 2:2 ligand,Zn2+ is formed five coordination structure with N and O atoms and the binding constant was 1016.8.3HC-DPA has good sensitivity and high selectivity of Zn2+ in solution.Cell experiments demonstrated that 3HC-DPA possessed the ability to monitor intracellular free zinc ions in live mammalian cells with better cell-permeable properties and longer mean cell retention time.Confocal laser scanning microscope and flow cytometry showed that it was potentially able to distinguish cancerous prostate cells from normal prostate cells,based on the the difference of the ability to uptake Zn2+ in normal cells and cancer cells.In addition,the activity of copper zinc superoxide dismutase(SOD1)in prostate cancer cells were higher was higher than normal prostate cells,we also synthesized the Zn2+ and H2O2 dual target fluorescent probe 3HC-2 to except to measure Zn2+ and H2O2 simultaneously,aiming to improve the sensitivity of fluorescence sensors.