Study On Platinum Diimine-based PDT Agents Loaded On Magnetic Nanocomposites

Cancer is a major threat to human health and its morbidity is increasing in recent yeas. The number of the people in the globe who die from cancer is expected to reach over 11 million in 2035. Thus, researchers all over the world have been engaged in finding ways to cure the disease. Currently, the ways to cure the cancer include the radiation therapy, the surgical therapy and the drug therapy. However, owing to their limit of applicability or severe side effects, the scientists have been trying to find better ways to cure the cancer. Photodynamic therapy (PDT) is just such a promising therapeutic modality.PDT is a new and effective method for cancer therapy. This approach is based on the local or systemic administration of a photosensitizer in tumor tissue followed by irradiation with visible light at an appropriate wavelength. The activated photosensitizer would produce the cytotoxic singlet oxygen or other reactive oxygen species in targeted cells, thereby initiating apoptotic and necrotic death of the tumor. The photosensitizer is the most important element for the Photodynamic Therapy. The structural modification of the photosensitizer could make the photosensitizer have longer maximum wavelength in the red light region and have more potent capability to generate singlet oxygen when irradiated with red light. Employing magnetite-silica composite nanoparticles as carriers of the photodynamic therapeutic agents would render the PDT agents better selectivity and improve their dispersibility in water.In this thesis, a series of platinum diimine complexes were synthesized, and their capability to generate singlet oxygen were studied. Then these complexes were loaded on different magnetic nanocomposite particles, and the interactions of the drug-loading magnetic nanocomposites with DNA or tumor cells were studied.l.Pt(OPDI)2, Pt(OPDI)(4-Br-OPDI) and Pt(OPDI)(4-TPA-OPDI) were synthesized and charactrized by elemental analysis, UV,’HNMR and IR.2.The photodynamic activity of the complexes was studied employing DPBF as a fluorescent probe. The results showed that Pt(OPDI) (4-TPA-OPDI) has good capability to generate singlet oxygen when irradiated with red light.3.(Fe3O4/CA)@SiO2, (Fe3O4/TA)@SiO2 and (Fe3O4/VC)@SiO2 were prepared. These magnetic nanoparticles were characterized by XRD. The size of (Fe3O4/TA)@SiO2, (Fe3O4/CA)@SiO2 or (Fe3O4/VC)@SiO2 is 10.21nm,14.3nm and 16.30nm, respectively.4.When each complex was loaded on the nanocomposites, the drug-loading capability was determined by UV-Vis spectra.5.The interactions of photosensitizer-loaded magnetic composite nanoparticles with pBR322DNA were investigated by agarose gel electrophoresis. The results show that the photosensitizer-loaded magnetic composite nanoparticles can generate singlet oxygen when irradiated with red light, leading to DNA damage.6.The interactions of photosensitizer-loaded magnetic composite nanoparticles with HepG-2 cell were investigated by MTT assay. The results show that the photosensitizer-loaded magnetic composite nanoparticles can lead to significant cell death when irradiated with red light.