National Technical University of Athens, Greece
Title: Effect of silver doped nanostructured titanium dioxide (TiO2) on breast cancer epithelial cells
Dr. Nefeli Lagopati studied Physics (BSc), Medical Physics (MSc), Advanced Materials (MSc) and Biology (PhD). She works as a postdoc researcher at the National Technical University of Athens, School of Chemical Engineering, and at Molecular Carcinogenesis Group, School of Medicine, University of Athens, where she additionally works as an adjunct lecturer, teaching “Cancer Biology”. Her research interests include the multidisciplinary field of nanomedicine in cancer treatment. Specifically, she focuses on the possible apoptotic effect of nanomaterials on breast cancer cells (IKY Scholarship). In the past, she had worked on (European) research projects, related to dosimetry in nuclear medicine, radiobiology - investigation of chromosomal alterations due to radiation, biochemistry of ROS-induced glutathionylation and evaluation of the role of iron ions, development of drug delivery systems and biomaterials, based on hydroxyapatite and chitosan, Monte Carlo Simulation etc. She is also a classical guitarist (BSc) and loves art and travelling
The scientific community approaches the multivariate condition of cancer disease in many ways. There are still aspects of the research field of alternative cancer treatments that remains to be discovered, focusing on minimize the undesirable consequences of the conventional treatment methods. It is now well established that when TiO2 nanoparticles are photo-excited, the photon energy generates pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) which can damage cancer cells. Therefore, TiO2 is a promising photosensitizer against cancer.
The aim of this study is the development of TiO2 nanoparticles with the potential to photo-induce anticancer effect via the mechanism of oxidative stress upon irradiation with visible light. Surface modification by doping with metal ions improves TiO2 photocatalytic activity. This process leads to reduction of electron-hole recombination, resulting in efï¬cient separation and stronger photocatalytic reactions. Particularly, silver is an important dopant, which up-regulates TiO2 biological activity.
Thus, Ag-doping of TiO2 was undergone, followed by detailed characterization (XRD, micro-Raman, SEM). Cultured MCF-7 and MDA-MB-468 breast cancer epithelial cells were irradiated, using visible light, in the presence of Ag-doped TiO2 aqueous dispersion. Cell viability was estimated, by MTT colorimetric assay. Western blot analysis of protein expression and characterization, as well as DNA laddering assay were used to investigate the existence of cell apoptosis.
We demonstrated that Ag-doped TiO2 nanoparticles induced apoptosis specifically in the highly malignant MDA-MB-468 cancer cells. MCF-7 cells were still unaffected, under the same circumstances. The molecular mechanism of TiO2 nanoparticles cytotoxicity was associated with increased pro-apoptotic Bax expression and caspase-mediated poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) activation thus resulting in DNA fragmentation and programmed cell death.
Further studies are already in progress, focalizing at the development of visible-light-excited co-doped TiO2 nanoparticles with silver and nitrogen, for targeted cancer therapy.