Studies On Amino-silane Modified Magnetic Nanocomposites As Drug Carriers For PDT Agents

Phtotodynamic therapy (PDT) is a new therapeutic modality for cancer treatment. This approach is based on the principle that the photosensitizer molecules which absorbed visible light would transfer energy to the oxygen molecules in tumor cells and generate cytotoxic singlet oxygen or other reactive oxygen species, which lead to apoptosis or necrosis of tumor cells. Most photosensitizers in current PDT applications are hydrophobic. They have poor water-solubility, low bioavailability and some side effects against normal cells. For this reason, aminosilane-modified magnetic nanocompo-sites employed as delivery vehicles for PDT agents have been studied in detail in this thesis, so as to improve the hydrophilicity of the photosensitizer meanwhile retaining its hydrophobicity. The following work has been carried out:(1) Fe3O4@SiO2 nanoparticles were firstly prepared, and then they were modified with two kinds of aminosilane to obtain magnetic nanocomposites Fe3O4@SiO2-APTES and Fe3O4@SiO2-AEAPS, which have better water-dispersibility and biocompatibility. The afforded nanocomposites were characterized by IR and XRD, and their values of zeta potential in water were also measured. The diameters for Fe3O4@SiO2-APTES and Fe3O4@SiO2-AEAPS were calculated as 11.94 nm and 12.85 nm, respectively. The values of Zeta potential for them were measured as 31.7 mV and 32.7 mV, respectively.(2) When Complex I or Complex II was loaded on the nanocomposites, the drug-loaded nanocomposites were afforded, whose drug-loading capacity was determined by UV-vis spectra. The results showed that when loaded with Complex I, the drug-loading capacity for Fe3O4@SiO2-APTES, Fe3O4@SiO2-AEAPS or (Fe3O4/TA)@SiO2 was 7.6%,7.4%,7.5%, respectively, whereas when loaded with Complex II, the drug-loading capacity for Fe3O4@SiO2-APTES, Fe3O4@SiO2-AEAPS or (Fe3O4/TA)@SiO2 was 8.4%,8.3%,8.5%, respectively.(3) DNA damage induced by the magnetic nanocomposites or the drug-loaded nanocomposites was studied by agarose gel electrophoresis. The results showed that the positively chareged nanocomposites, such as Fe3O4@SiO2-APTES or Fe3O4@SiO2-AEAPS, could hardly induce DNA damage, whereas the negatively charged nanocomposites, such as (Fe3O4/TA)@SiO2, could induce DNA damage to some extent. When loaded with the photosensitizer, the above-mentioned three kinds of nanocomposites could all induce DNA damage to some extent when irradiated with light, and the extent of DNA damage correlated positively with the amount of the drug-loaded nanocomposites employed.(4) The in vitro antitumor activity of the photosensitizers and the drug-loaded nanocomposites when irradiated with red light were investigated by MTT assay. The results showed that the photosensitizers and the drug-loaded nanocomposites could all inhibit the proliferation of the tumor cells to some extent when irradiated with red light. The inhibition rate depended on the photosensitizer or the drug-loaded nanocomposites employed. As far as the inhibition rate of the drug-loaded nanocomposites against the tumor cells, the positively charged drug-loaded nanocomposites behaved better than the negatively charged ones.(5) After irradiation with red light, the impact of the photosensitizers or the drug-loaded nanocomposites on the cycles of MCF-7 cells was investigated by the flow cytometric assay. The results suggested that both the irradiated phosensitizers and the drug-loaded nanocomposites could retard the cell cycles, inhibiting the proliferation rate of the tumor cells.