Room: Stars at Night Ballroom 1
Purpose: Glioblastoma is the most common primary brain tumor in adults and yet it remains one of the least treatable. Current standard of care which involves combinations of surgery, radiotherapy and chemotherapy, results in a median survival of only 15 months. This dismal outcome is partly due to the high radio-resistance of Glioblastoma. The purpose of this work is to develop strategies that will ultimately enhance radiotherapy outcomes for glioblastoma through radiosensitization.
Methods: Having recently published our novel assay wherein we used fluorescence intensity modulation of PEGylated (biocompatible) CdSe/ZnS quantum dots (QDs) to assess reactive oxygen species (ROS) generation during chemotherapy and radiotherapy for cancer cells, we are applying this assay for concurrent measurement of ROS and radiosensitization. Using a Faxitron Cell Irradiator, we irradiate brain cancer cells (T98G Glioblastoma cells) treated with QDs and measure both their migration and the QD fluorescence intensity. We measure and quantify the migration using a commercially available Electric Cell Impedance Sensor (ECIS).
Results: Irradiated T98G cells attach and migrate significantly (p<0.0001) more than non-irradiated cells in the first 20 hours post irradiation. Preliminary results also show that the radiotherapy leads to QD intensity reduction due to ROS production as expected. Results for radiosensitization using QDs will be presented. Furthermore, we found highly significant (p < 0.0001) modulation of the photophysical properties of PEGylated CdSe/ZnS by ROS from therapeutic concentrations of common chemotherapy drugs, Doxorubicin and Daunorubicin.
Conclusion: We have developed an assay for the in vitro concurrent measurement of ROS and radiosensitization with possible application in concurrent imaging and drug delivery. This suggests using PEGylated QDs and similar conjugates as biophysical assays for the development of in vivo strategies that will enhance radiotherapeutic outcomes for glioblastoma and other highly radio-resistant tumors.