In Vitro and In Vivo Synergetic Radiotherapy with Gold Nanoparticles and Docetaxel for Pancreatic Cancer

Author:

Alhussan Abdulaziz1ORCID,Jackson Nolan1,Chow Norman2ORCID,Gete Ermias34,Wretham Nicole2,Dos Santos Nancy2,Beckham Wayne15,Duzenli Cheryl34ORCID,Chithrani Devika B.15678ORCID

Affiliation:

1. Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada

2. Department of Experimental Therapeutics, British Columbia Cancer-Vancouver, Vancouver, BC V5Z IL3, Canada

3. Radiation Oncology, British Columbia Cancer-Vancouver, Vancouver, BC V5Z 4E6, Canada

4. Department of Physics and Astronomy, University of British Columbia, Vancouver, BC V6T 1Z1, Canada

5. Radiation Oncology, British Columbia Cancer-Victoria, Victoria, BC V8R 6V5, Canada

6. Center for Advanced Materials and Related Technologies, Department of Chemistry, University of Victoria, Victoria, BC V8P 5C2, Canada

7. Department of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada

8. Department of Computer Science, Mathematics, Physics and Statistics, Okanagan Campus, University of British Columbia, Kelowna, BC V1V 1V7, Canada

Abstract

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 μg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.

Funder

Kuwait Foundation for the Advancement of Sciences

NanoMedicines Innovation Network Strategic Initiative fund

John R. Evans Leaders Fund

British Columbia Knowledge Development Fund

Discovery Grant from the Natural Sciences and Engineering Research Council of Canada

National Institutes of Health (NIH) of the United States of America

University of Victoria

Publisher

MDPI AG

Reference54 articles.

1. Cancer statistics. 2022;Siegel;CA A Cancer J. Clin.,2022

2. Pancreatic Cancer: A Review of Current Treatment and Novel Therapies;Kolbeinsson;J. Investig. Surg.,2023

3. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes;McGuigan;World J. Gastroenterol.,2018

4. Pancreatic cancer;Vincent;Lancet,2011

5. Epidemiology of pancreatic cancer;Ilic;World J. Gastroenterol.,2016

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