Abstract
Purpose: Glioblastoma remains the most malignant and most common primary brain tumor in adults, with a median overall survival of only 15 months. This bleak outcome is partly due to the high chemoresistance and high radioresistance of glioblastoma. Current standard of care includes surgical resection, chemotherapy and temozolomide (TMZ) as adjuvant therapy. The purpose of this work is to improve treatment outcomes for highly radioresistant and chemoresistant cancers employing nanoparticle mediated radiosensitization and chemoradiotherapy. Methods: We are using nanoparticle (NP) spectroscopy with a broad range of novel biocompatible nanoparticles including carbon quantum dots (CQD), graphene quantum dots (GQD), and CdSe/Zns quantum dots (QD) based on our recently developed assay involving fluorescence intensity modulation of QDs to assess reactive oxygen species (ROS) generation during chemotherapy and radiotherapy. Our strategy here is to use the NPs for concurrent measurement of ROS and radiosensitization, while applying chemoradiotherapy. We also have a focus on clonogenic assays for cell lines treated with this same broad range of quantum dots with (TMZ) for measurement of cell survival two- and three-weeks posttreatment. Using a standard laboratory cell irradiator (Faxitron), we irradiate glioblastoma cancer cell lines (T98G and U87 cells) treated with QDs, CQDs, and GQDs as well as chemotherapeutic drugs such as Temozolomide (TMZ).
Results and Conclusions: Cell survival curves from clonogenic assays show an increase (p < 0.0001) in cell death with an increase in radiation, but no statistically significant difference in survival fraction when either nanoparticles, temozolomide, or both are added. Focusing on changes in α/β ratio between radiation alone, radiation with radiosenstizers, and radiation with radiosenstitizers and temozolomide, we see that there is not much therapeutic gain. Although cell survival curves did not show a significant increase in cell death, ECIS results show that there may be a decrease in migration and local invasion. This decrease in migration and local invasion may aid in reducing reoccurrence, a major contributor in death resulting from glioblastoma. The hypothesis is confirmed that we can use changes in clonogenic parameters, migration, and morphometry to find out effects of quantum dot radiosensitization and chemoradiotherapy on glioma cells in vitro. The cell killing effects of quantum dots and chemoradiotherapy are not as expected, but the reduction in migration with quantum dots is a possible indication of anti-metastatic potential of quantum dots with chemotherapy, which should be further investigated.