|dc.description.abstract||Radiation therapy is a principal modality in many cancer treatments. However, highly radioresistant forms of cancer, such as glioblastoma multiforme, present a significant clinical challenge resulting in poor prognoses. Over the past decade, new forms of radiation therapy have emerged in the form of nanoparticle-mediated radiation therapy. Research of this promising new modality suggests enhanced therapeutic effects of ionizing radiation through local tumor dose enhancement and radiosensitization. This is attributed to the release of secondary electrons amplifying the generation of reactive oxygen species (ROS) that damage intracellular targets, such as DNA, within their immediate vicinity. Additionally, functionalization of various nanoparticles to target malignant cells and organelles within cells to localize enhancement of ROS and subsequently tumor dose. The amalgamation results in a more favorable therapeutic index by improving tumor control probability.
The objective of this work is to improve radiation therapy outcomes for glioblastoma through local dose enhancement and radiosensitization. We have recently published our novel assay employing CdSe/ZnS quantum dots as probes for ROS generation during chemotherapy and radiation therapy for cancer cells through fluorescence intensity modulation. We apply this method for concurrent measurements of ROS and radiosensitization for PEGylated (biocompatible) CdSe/ZnS, carbon quantum dots (CQD), and graphene quantum dots (GQD). Using a compact Faxitron Cell Irradiator and clinical Siemens Oncor linear accelerator (LINAC), we irradiated U87 and T98G glioblastoma derived cells inoculated with nanoparticles and measured their migratory behavior and quantum dot fluorescence intensity. Cell attachment, migration, and proliferation are quantified through commercially available Electric Cell-substrate Impedance Sensing (ECIS) measurements. Clonogenic assays were employed to obtain cell survival curve as another method to quantify the dose enhancement factor of our nanoparticles.
Irradiated T98G glioblastoma cells attached and migrated significantly more than non- irradiated cells. Graphene quantum dots (GQD) showed radiosensitization and anti- metastatic properties through significantly decreased migration at both 5 Gy and 20 Gy. The calculated dose enhancement factor (DEF) for ECIS measurements were 1.5 ± 0.2 and 1.4 ± 0.1 for 5 Gy and 20 Gy respectively. This was consistent with cell survival curve DEF calculation of 2.01 ± 0.03. DEF calculations suggest GQDs are effective radiosensitizers. This is supported by Relative peak fluorescence intensity (RPFI) ratio of 2000 ± 400% and 1800 ± 700% indicating enhanced secondary electron production leading to amplified ROS generation at both 5 Gy and 20 Gy respectively. RPFI ratio for U87 were 400 ± 70% and 1100 ± 300% for 5 Gy and 20 Gy also indicating enhanced ROS production.||en_US