Phosphorescent Transition Metal Complexes For Hypoxia Imaging And Photodynamic Therapy

Recently,the incidence and mortality of cancer has surpassed that of cardiovascular disease,becoming a serious threat to people’s health and life.Detection and therapy of tumour are of great significance.Phosphorescent transition metal complex shows large Stokes Shifts,long luminescence lifetime,high stability,and great sensitivity to environments,which exhibits abundant excited states and excellent biocompability,and has been widely used in bioimaging,detection and therapy.This thesis focuses on the applications of two phosphorescent transition metal complexes in hypoxia detection and photodynamic chemotherapy.The main content includes the following parts:1.Design,synthesis and application of an iridium(Ⅲ)complex for hypoxia detection and photodynamic therapyIn order to realize the detection and treatment of tumors,an iridium(Ⅲ)complex Ir1 with functions of hypoxic detection and photodynamic therapy is designed and synthesized.Along with the decrease of oxygen concentration,the emission intensity and luminescence lifetime of the complex significantly increase,showing obvious responsive to oxygen concentration.In cellular experiments,Ir1 shows low cytotoxicity for living cells cultured in dark.High photocytotoxicity is achieved when the cells were exposed to light,suggesting that the complex can be used for photodynamic therapy.Confocal fluorescence imaging proves that the complex concentrates in the mitochondria.In addition,the luminescence lifetime of Ir1 under hypoxic environment is significantly improved compared to that in normoxia.Further study showed that Ir1 can produce singlet oxygen under irradiation,causing significant damage to cell and good photodynamic therapy effect.2.A cell membrane-targeted ruthenium(Ⅱ)complex for imaging and photodynamic therapyIn order to achieve the therapy of tumors,Ru1,a cell membrane-targeted ruthenium(Ⅱ)complex is designed and synthesized for photodynamic therapy.This complex shows high phosphorescent quantum yield and singlet oxygen quantum yield in solution,low cytotoxicity and excellent cell membrane targeting property.Photoexcitation of a low dose of Ru1 on the cell membrane can relax the protection of the cells against extracellular molecules and increase the permeability.He La cells treated with Ru1 followed by irradiation and incubation with Ir2 significantly enhance the green luminescence of Ir2.Furthermore,Ru1 can assist cisplatin,a chemotherapy drug,in internalization into cancer cells,and thus improve the chemotherapy efficacy,reduce the dosage,showing a good photodynamic therapy performance.