Nanoparticle Enhanced X-Ray Therapy (Developmental Collaborator-Driven Research Project)
UCD Chemistry: T Guo, Y Qu; UCD Radiation Oncology: R Yunis, A Vaughan; CBST: FYS Chuang
Radiation therapy is the most effective method for treating tumors of the brain. The primary mechanism of ionizing radiation therapy is the production of free radicals that disrupt chemical bonds in DNA, causing irreparable damage and fragmentation of the molecule. In current clinical application, however, the relative yield of therapeutic DNA damage, in proportion to the amount of radiation dose delivered, appears to be small and not particularly selective for cancer cells versus normal healthy cells. Having demonstrated a 200% enhancement of radiation damage to purified strand of DNA in vitro, with only ten 3 nm gold nanoparticles attached to it – we propose that functionalized gold nanoparticles (AuNP) may be useful in enhancing the cytotoxic effect of radiation therapy, as well as concentrate the effect on targeted tumor cells in tissue. By demonstrating this effect on cultured tumor cell lines, we have the following aims: (1) assess the mechanism of uptake and distribution of AuNP in living cells; (2) verify the mechanism of cytotoxicity in tumor cells; and (3) determine whether radiation damage is caused by a direct or indirect effect of ionizing reactions in the cell.
Using a medulloblastoma-derived cell line, Daoy – we used confocal fluorescence microscopy to observe the uptake of FITC-conjugated AuNP. Three hours of passive incubation was sufficient for AuNP uptake by the cells. To determine the increase in efficacy of radiation-induced damage, cells were treated with different concentrations of AuNPs for 24 hours prior to exposure to varying doses of ionizing radiation. We observed that negatively-charged mercaptoundecanoic acid (MUA)-AuNP exhibited high rates of cell killing. The positively-charged TMA-AuNP had an effect which was dependent on radiation dose and cell density. While more work needs to be done to determine the mechanism of enhancement by AuNP on the effect of radiotherapy, we have demonstrated and confirmed with a cellular model that AuNP indeed may be an important and useful nanotechnology for cancer medicine.