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Uptake and Retention of Radiosensitizing Nanoparticles in Key Cells of a Pancreatic Tumor Microenvironment

A Alhussan1*, D Chithrani1, W Beckham2, K Bromma1, (1) University of Victoria, Victoria, BC, CA, (2) BC Cancer Agency- Vancouver Island Centre, Victoria, BC, CA

Presentations

WE-IePD-TRACK 3-6 (Wednesday, 7/28/2021) 5:30 PM - 6:00 PM [Eastern Time (GMT-4)]

Purpose: Pancreatic cancer is one of the deadliest types of cancer with a 5-year survival rate of only 10%. Nanotechnology offers a novel perspective to treat such deadly cancers through their incorporation into radiotherapy and chemotherapy. However, the interaction of nanoparticles (NPs) with cancer cells and with other major cell types within the pancreatic tumor microenvironment (TME) is yet to be understood. Therefore, our goal is to shed the light on the dynamics of NPs within a TME of pancreatic origin.

Methods: In addition to cancer cells, normal fibroblasts (NFs) and cancer associated fibroblasts (CAFs) were examined in this experiment due to their important yet opposite roles of suppressing tumor growth and promoting tumor growth, respectively. We used gold nanoparticles as the model NP system due to their biocompatibility and physical & chemical proprieties, and their dynamics were studied both quantitatively and qualitatively in vitro and in vivo.

Results: The in vitro studies revealed that both cancer cells and CAFs take up 50% more NPs compared to NFs. Most importantly, they all managed to retain 70-80% of NPs over a 24-hour time period. Uptake and retention of NPs within an in vivo environment was also consistent with in vitro results.

Conclusion: The experiment concludes that NP-based targeting of both tumor cells and CAFs could be used as a smart novel strategy towards improving current anti-cancer therapies.

Funding Support, Disclosures, and Conflict of Interest: Authors would like to acknowledge Natural Sciences and Engineering Research Council of Canada, British Columbia Knowledge Development Fund and Canadian Foundation for Innovation for their support.

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