Potential of gold nanoparticles in current radiotherapy using a co-culture model of cancer cells and cancer associated fibroblasts
Date
2022
Authors
Alhussan, Abdulaziz
Palmerley, Nicholas
Smazynski, Julian
Karasinska, Joanna
Renouf, Daniel J.
Schaeffer, David F.
Beckham, Wayne
Alexander, Abraham S.
Chithrani, Devika B.
Journal Title
Journal ISSN
Volume Title
Publisher
Cancers
Abstract
Many cancer therapeutics are tested in vitro using only tumour cells. However, the tumour
promoting effect of cancer associated fibroblasts (CAFs) within the tumour microenvironment (TME)
is thought to reduce cancer therapeutics’ efficacy. We have chosen pancreatic ductal adenocarcinoma
(PDAC) as our tumor model. Our goal is to create a co-culture of CAFs and tumour cells to model the
interaction between cancer and stromal cells in the TME and allow for better testing of therapeutic
combinations. To test the proposed co-culture model, a gold nanoparticle (GNP) mediated-radiation
response was used. Cells were grown in co-culture with different ratios of CAFs to cancer cells.
MIA PaCa-2 was used as our PDAC cancer cell line. Co-cultured cells were treated with 2 Gy of
radiation following GNP incubation. DNA damage and cell proliferation were examined to assess the
combined effect of radiation and GNPs. Cancer cells in co-culture exhibited up to a 23% decrease in
DNA double strand breaks (DSB) and up to a 35% increase in proliferation compared to monocultures.
GNP/Radiotherapy (RT) induced up to a 25% increase in DNA DSBs and up to a 15% decrease
in proliferation compared to RT alone in both monocultured and co-cultured cells. The observed
resistance in the co-culture system may be attributed to the role of CAFs in supporting cancer cells.
Moreover, we were able to reduce the activity of CAFs using GNPs during radiation treatment.
Indeed, CAFs internalize a significantly higher number of GNPs, which may have led to the reduction
in their activity. One reason experimental therapeutics fail in clinical trials relates to limitations in the pre-clinical models that lack a true representation of the TME. We have demonstrated a co-culture
platform to test GNP/RT in a clinically relevant environment.
Description
Keywords
MIA PaCa-2, cancer associated fibroblasts, co-culture, monoculture, gold nanoparticle, pancreatic cancer, nanotechnology, radiosensitization, Centre for Advanced Materials and Related Technologies (CAMTEC), Centre for Biomedical Research
Citation
Alhussan, A., Palmerley, N., Smazynski, J., Karasinska, J., Renouf, D., . . . Chithrani, D. (2022). “Potential of gold nanoparticles in current radiotherapy using a co-culture model of cancer cells and cancer associated fibroblasts.” Cancers, 14(15), 3586. https://doi.org/10.3390/cancers14153586