Design And Synthesis Of Probes For Intracellular Reducing Molecules And Photodynamic Therapy

A variety of oxidizing and reducing agents jointly maintain the redox environment in cells. Organisms will suffer from various kinds of physiological diseases, such as tumor when redox status is abnormal. Additionally, reactive oxygen species, such as singlet oxygen is cytotoxic, so that cancer cells can be killed by photodynamic therapy. Compared with the traditional organic fluorescent molecules with short lifetime, phosphorescent iridium complexes can conquer background fluorescent interference because of their long emission lifetime and good photostability and show a promise in biological detection and imaging. With the development of nano-technology and nano-medicine, organic-inorganic hybrid silicon nanomaterials have good biocompatibility, playing an important role in biological imaging. In this thesis, we synthesized a kind of phosphorescent iridium complexe with nitroxide radical, and studied the photophysical properties of iridium complexe and application in detecting the intracellular reducing molecules. Additionally, we prepared mesoporous silica-porphyrin hybrid nanomaterials dispersed in water, and studied their application in biological imaging and photodynamic therapy. The main contents are as follows:Firstly, a kind of phosphorescent iridium complexe Ir-NO with 2, 2, 6, 6-tetramethylpiperidine-1-oxyl(TEMPO) radical has been designed and synthesized. TEMPO serving as responsive group to reductant is introduced into N^N ligand structure to change of photophysical properties of iridium complexes. Upon addition of reducing molecules, the emission intensity of Ir-NO is turned on, and lifetime is elongated as well. Confocal imaging and phosphorescence lifetime imaging have also been used for detecting the intracellular reducing molecules. The luminescence signal in cancer cells is stronger than normal cells, because of the redox state in cancer cells; What’s more, luminescence intensity in cells incubated with reducing molecules is enhanced obviously and lifetime is elongated. Therefore, iridium complexe Ir-NO has been successfully applied in detecting the intracellular reducing molecules.Secondly, mesoporous silica-porphyrin hybrid nanomaterials(MSPHNs) have been prepared. The diameter of MSPHNs is about 45 nm and they can be well-dispersed in water. FTIR shows that porphyrin molecular(TCPP) is introduced into the silicon frame through covalent bond. The characterization of MSPHNs for their partical size, large surface area and uniform mesoporous pore is measured by TEM,DLS and N2 adsorption isotherm, etc. The encapsulation by silicon frame and heavy atom effect can effectively improve the Q band of TCPP, leading to improve the efficiency of singlet oxygen. The application of MSPHNs in photodynamic therapy for tumor cells is explored. Confocal imaging shows that MSPHNs can produce the cytotoxic singlet oxygen and induce the apoptosis of He La cells. Thus MSPHNs have a great potential in photodynamic therapy for tumor cells.