Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model
Abdulaziz Alhussan1, Nolan Jackson1, Reinali Calisin1
1Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada.
Abstract:
Pancreatic cancer stands among the deadliest forms of cancer, and the existing treatments fall short of providing adequate efficacy. Novel and more effective treatment approaches are urgently required to address this critical medical challenge. In this study, we aimed to evaluate the anti-cancer efficacy of gold nanoparticles (GNPs) in combination with radiotherapy (RT). A 3D pancreatic cancer co-culture spheroid model of MIA PaCa-2 cancer cells and patient-derived cancer-associated fibroblasts (CAF-98) was used. The spheroids were treated with GNPs (7.5 μg/mL) and 2 Gy of RT. The spheroids' cell viability was assessed through the CellTiter-Glo 3D assay, and an immunofluorescence assay was used to assess the DNA DSBs via the expression of the DNA damage marker 53BP1. Co-culture samples showed a 10.8% (p < 0.05) increase in proliferation and a 13.0% (p < 0.05) decrease in DNA DSB when compared to monoculture samples, However, they displayed a 175% (p < 0.001) increase in GNPs uptake when compared to monoculture spheroids. Using GNPs/RT, we were able to show a significant reduction of 6.2% (p < 0.05) in spheroid size and an increase of 14.3% (p < 0.05) in DNA DSB damage in co-culture samples. The combination of GNPs with RT demonstrated remarkable radiosensitization effects, representing a promising approach to enhance cancer treatment efficacy. These effects were particularly noteworthy in the more treatment-resistant co-culture spheroid model.
Insights
This study explored gold nanoparticles (GNPs) combined with radiotherapy (RT) to treat pancreatic cancer. The combination significantly reduced tumor size and increased DNA damage, showing promise for more effective cancer therapy.
Area of Science:
- Oncology
- Nanomedicine
- Radiotherapy
Background:
- Pancreatic cancer has poor treatment outcomes, necessitating novel therapeutic strategies.
- Current treatments lack sufficient efficacy, highlighting the urgent need for advanced approaches.
- Gold nanoparticles (GNPs) offer potential as radiosensitizers in cancer therapy.
Purpose of the Study:
- To evaluate the anti-cancer efficacy of combining gold nanoparticles (GNPs) with radiotherapy (RT).
- To assess the radiosensitization effects of GNPs in a 3D pancreatic cancer co-culture model.
- To investigate the impact of GNPs and RT on cancer cell viability and DNA damage.
Main Methods:
- Utilized a 3D pancreatic cancer co-culture spheroid model (MIA PaCa-2 cells and CAFs).
- Treated spheroids with GNPs (7.5 μg/mL) and 2 Gy of RT.
- Assessed cell viability using CellTiter-Glo 3D assay and DNA double-strand breaks (DSBs) via 53BP1 expression.
Main Results:
- Co-culture spheroids exhibited increased proliferation and decreased DNA DSBs compared to monocultures.
- Co-culture spheroids showed significantly higher GNP uptake (175%) than monocultures.
- The combination of GNPs/RT reduced spheroid size by 6.2% and increased DNA DSBs by 14.3%.
Conclusions:
- The combination of GNPs with RT demonstrated significant radiosensitization effects in pancreatic cancer spheroids.
- This approach shows promise for enhancing the efficacy of radiotherapy in cancer treatment.
- The findings are particularly relevant for treatment-resistant co-culture models, suggesting broader applicability.
