Purpose: Although glioblastoma is the most common primary brain tumor in adults, it remains one of the least treatable. The median survival is only 15 months following current standard of care which includes combinations of surgery, radiotherapy, and chemotherapy. 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 developed and published a novel assay using 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 have added other nanoparticles to this assay and are applying it for concurrent measurement of ROS and radiosensitization. Using a Faxitron Cell Irradiator, we irradiate (5 Gy, 10 Gy, 20 Gy, 50 Gy) glioblastoma cancer cell lines (T98G and U87 cells) treated with QDs and carbon quantum dots (CQD) and measure both their QD/CQD fluorescence intensity and their migration. We measure and quantify the migration using a commercially available Electric Cell Impedance Sensor (ECIS).
Results: U87 and T98G cells attach and migrate significantly (p<0.0001) more than non-irradiated cells in the first 20 hours post-irradiation with 20 Gy. Our results show QD intensity reduction due to ROS production as expected, but intensity enhancement for CQD. Furthermore, relative peak fluorescence intensity ratio calculations and average intensity comparisons show highly significant (p<0.001) enhancement of ROS for 5 Gy and 20 Gy irradiation.
Conclusion: We have developed a nanoparticle-based assay for in vitro concurrent measurement of ROS and radiosensitization of cancer cells. This suggests using PEGylated QDs, CQDs and similar conjugates to improve radiotherapeutic outcomes for glioblastoma and other highly radio-resistant tumors.
Brain, Radiosensitivity, Radiation Therapy