Studies On Diagnosis And Treatment Of Tumor Cells Based On Iridium(?) And Ruthenium(?) Complex Sensors

Phosphorescent transition metal complexes exhibit long-lived triplet excited states,which can not only show phosphorescence,but also generate reactive oxygen species(ROS)to damage tumor cells.Therefore,they have attracted a lot of attention in the fields of sensing,cell imaging and photodynamic therapy(PDT).Due to the strong oxidability,peroxynitrite(ONOO^-)plays an important role in intracellular signal transduction and maintenance of REDOX homeostasis.While abnormal levels of ONOO^-affects physiological functions of cells and may cause a variety of diseases.As a result,it is helpful for early diagnosis of disease to develop methods for monitoring ONOO^-in vivo.The clinical application of PDT has increased greatly in recent years due to the advantages of spatio-temporal selectivity,non-invasions,low drug resistance and low cytotoxicity.However,type?photosensitizers cannot produce singlet oxygen(~1O₂)under hypoxia,the PDT effect in hypoxic tumors is badly limited.To solve these problems,we designed a class of probes and photosensitizers based on phosphorescent iridium and ruthenium complexes to detect ONOO^-in tumor cells and treat tumor in hypoxia.The content of this dissertation mainly includes the following four parts:Chapter 1:The research background and progress of phosphorescent transition metal complexes in the field of sensing and PDT have been briefly introduced.The research progress of phosphorescent probes and photosensitizers based on iridium(?)and ruthenium(?)complexes was summarized emphatically.Chapter 2:A phosphorescent probe of ruthenium(?)complex was designed in which C=C unsaturated double bond was used as the response site of ONOO^-and a N-substituted indole salt was used as the luminescence quenching group.The probe showed enhanced phosphorescence towards ONOO^-,and could quickly,sensitively and selectively recognize ONOO^-in vitro.The probe showed great application potential in time-resolved luminescence detection,two-photon absorption and cell imaging.Chapter 3:An iridium(?)complex photosensitizer was synthesized by changing the central metal.The photosensitizer could generate reactive oxygen species through type?and type?mechanisms simultaneously,reducing the dependence on oxygen.The photosensitizer showed great cytotoxicity to He La cells under light and it mainly concentrated in mitochondria,which could destroy mitochondria of tumor cells in the first time and achieve efficient photodynamic therapy effect.Since the complex itself was oxidized by ROS produced under light and then turned on phosphorescence,the treatment process could be monitored in real time through cell imaging.Therefore,the photosensitizer was expected to be used in the diagnosis and treatment of tumor cells simultaneously.Chapter 4:An iridium(?)complex phosphorescent probe was synthesized to detect ONOO^-by simplifying the structure of ligand based on the above parts.The ligand structure of the probe is simpler and the reaction site is closer to the luminescence unit.The probe showed enhanced phosphorescence and had good selectivity towards ONOO^-.In addition,the probe also showed good imaging ability for endogenous ONOO^-and showed mitochondrial targeting ability.