Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model
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 eff...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12523 |
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| author | Abdulaziz Alhussan Nolan Jackson Reinali Calisin Jessica Morgan Wayne Beckham Devika B. Chithrani |
| author_facet | Abdulaziz Alhussan Nolan Jackson Reinali Calisin Jessica Morgan Wayne Beckham Devika B. Chithrani |
| author_sort | Abdulaziz Alhussan |
| collection | DOAJ |
| description | 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% (<i>p</i> < 0.05) increase in proliferation and a 13.0% (<i>p</i> < 0.05) decrease in DNA DSB when compared to monoculture samples, However, they displayed a 175% (<i>p</i> < 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% (<i>p</i> < 0.05) in spheroid size and an increase of 14.3% (<i>p</i> < 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. |
| first_indexed | 2024-03-11T00:24:33Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:24:33Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-920369dae21b4936b09843557cd5ffe42023-11-18T23:06:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151252310.3390/ijms241512523Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture ModelAbdulaziz Alhussan0Nolan Jackson1Reinali Calisin2Jessica Morgan3Wayne Beckham4Devika B. Chithrani5Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, CanadaDepartment of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, CanadaPancreatic 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% (<i>p</i> < 0.05) increase in proliferation and a 13.0% (<i>p</i> < 0.05) decrease in DNA DSB when compared to monoculture samples, However, they displayed a 175% (<i>p</i> < 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% (<i>p</i> < 0.05) in spheroid size and an increase of 14.3% (<i>p</i> < 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.https://www.mdpi.com/1422-0067/24/15/12523gold nanoparticlesradiosensitizers3D spheroidsco-culturepancreatic cancer |
| spellingShingle | Abdulaziz Alhussan Nolan Jackson Reinali Calisin Jessica Morgan Wayne Beckham Devika B. Chithrani Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model International Journal of Molecular Sciences gold nanoparticles radiosensitizers 3D spheroids co-culture pancreatic cancer |
| title | Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model |
| title_full | Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model |
| title_fullStr | Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model |
| title_full_unstemmed | Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model |
| title_short | Utilizing Gold Nanoparticles as Prospective Radiosensitizers in 3D Radioresistant Pancreatic Co-Culture Model |
| title_sort | utilizing gold nanoparticles as prospective radiosensitizers in 3d radioresistant pancreatic co culture model |
| topic | gold nanoparticles radiosensitizers 3D spheroids co-culture pancreatic cancer |
| url | https://www.mdpi.com/1422-0067/24/15/12523 |
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