Purpose: Despite the advancements in medicine in the last decade, pancreatic cancer is still one of the deadliest types of cancers with a survival rate of less than 7%. The location of pancreas in close proximity to many vital organs renders existing doses of radiotherapy (RT) inadequate for many patients. Gold nanoparticles (GNPs) have radiosensitizing properties and could also be used as a drug carrier to precisely deliver drugs to their target. In this paper, the radiosensitization effect of GNPs in co-cultures vs monoculture of cancer cells and Cancer associated fibroblasts (CAFs) is investigated.
Methods: Cells were grown in both monocultures and co-cultures then they were dosed with GNPs before being irradiated (2 Gy). GNPs were functionalized with Polyethylene glycol (PEG) and RGD peptide to specifically target cancerous cells. DNA DSB damage and proliferation assays were performed. Cells grown in co-culture were then separated using magnetic beads separation before being processed for GNP content.
Results: When combined with ionizing radiation, GNPs show radiosensitization effects superior to using radiation alone in both monoculture and co-culture cells. Cells grown in co-culture show lower DNA DSB damage, higher proliferation, and lower GNP content per cell compared to cells grown in monoculture. There seem to be a resistant in co-culture systems compared to monoculture systems.
Conclusion: The radiosensitization of GNPs is evident in both monocultures and co-cultures of hard-to-treat cancers opening the door for a combined treatment modality more effective compared to current RT. The apparent resistant in co-culture systems is attributed to the role of CAFs in supporting cancer cells and creating a more complex tumor microenvironment (TME). That could be the reason why many drugs fail in vivo and in clinical trials since their monoculture testing is lacking in reflecting many of the real TME properties.
Funding Support, Disclosures, and Conflict of Interest: Acknowledging the support of BC Cancer, Nanomedicines Innovation Network Strategic Initiative (NMIN-SI), John R. Evans Leaders Fund (JELF) from Canada Foundation for Innovation (CFI) and British Columbia Knowledge Development Fund (BCKDF), Kuwait Foundation for the Advancement of Sciences (KFAS), and the Natural Sciences and Engineering Research Council of Canada (NSERC).
Not Applicable / None Entered.