Radiosensitizing Prostate Cancer Though the Simultaneous Administration of Gold Nanoparticles and Chemotherapeutics
Abstract
Purpose
Radiotherapy with a 6 MV linear accelerator is extensively employed in cancer treatment, particularly for targeting deep-seated tumors. In our work, we have focused on maximizing the dose that can be safely delivered to patients. Our primarygoal is to optimize the radiation dose by combining it with radiosensitizing agents that have complementary effects. This approach aims to enhance the effectiveness of radiotherapy, allowing for increased doses to the tumor while minimizing the risk of additional side effects
Methods
A battery of assays were performed on human PC3 and LNCaP prostate cancer cell lines in vitro. GNP uptake and retention of was measured using inductively coupled plasma mass spectrometry. Cell cycles were then analyzed using Flow Cytometry. DNA double strand break (DSB) assays quantified DNA damage enhancement. All assays included testing control, GNP-only, chemotherapy-only, and combined GNP + chemotherapy.
Results
Adding a chemotherapy drug increased GNP uptake by 34% and retention by 148%. Live-cell confocal images of drug-treated cells showed microtubule stabilization and multinucleation, markers for cellular arrest in the radiosensitive G2/M phase of the cell-cycle. This result was confirmed by Flow Cytometry, which found a larger cell population in the G2/M phase at the 24 h timepoint for cells that had been treated with chemotherapy. Finally, a 50% increase in the number of DNA DSBs was observed for combined GNP + chemotherapy treatments.
Conclusion
The combined administration of chemotherapy and GNPs enhances the radiosensitivity of cancer cells by promoting increased uptake and retention, inducing cell cycle arrest in the radiosensitive, G2/M phase, and leading to cell death. The synergistic effect of GNPs and chemotherapeutic agents holds significant promise for significantly improving the effectiveness of radiation therapy. Future research will focus on identifying the most effective combination treatment strategies to optimize therapeutic outcomes.