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Work in our laboratory has focused on the development of TiO2-DNA nanocomposites for cancer therapy by gene removal. These nanocomposites are composed of 4.5 nanometer TiO2 nanoparticles, coated with glycidyl isopropyl ether that have conjugated to them oligonucleotide DNA(s). Within the nanocomposites, DNA oligonucleotides retain their base-pairing specificity, while the TiO2 nanoparticles exhibit their characteristic photoreactivity. Furthermore, TiO2 nanocomposites exhibit semiconducting properties through both constituents_excitation of TiO2 (by exposure to electromagnetic radiation of energy above 3.2 eV, 390 nm) results in charge separation ultimately causing irreversible proton trapping in the sugar molecules of the DNA phosphodiester backbone leading to the cleavage of the DNA. This endonuclease-like activity is: i) excitable by a factor not naturally encountered by the cells in vivo (electromagnetic radiation of energy higher than 3.2 eV); and ii) highly sequence specific_to the degree that it can be directed toward a single target in a whole genome (due to the high specificity of long oligonucleotide base-pairing). For the experiments described here we used cultured breast cancer MCF7 cells, and transfected them with TiO2-oligonucleotide nanocomposites specific to ribosomal DNA (a portion of the chromosomes called satellite DNA). In initial experiments we used X-ray fluorescence and electron microscopy to establish localization of the TiO2-DNA nanoparticles to ribosomal sites within the cells. We then excited the TiO2 nanoparticles by exposure to white light, causing the scission of ribosomal DNA. This rendered MCF7 cells unable to go through protein synthesis, and, eventually, led to their demise. We will present data demonstrating the distribution of TiO2-oligonucleotide nanocomposites in MCF7 cells 24 hours following electroporation, and describe the DNA scission experiments.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]