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

• Published in: Pharmaceutics
• Main Authors: Abdulaziz Alhussan, Nolan Jackson, Norman Chow, Ermias Gete, Nicole Wretham, Nancy Dos Santos, Wayne Beckham, Cheryl Duzenli, Devika B. Chithrani
• Format: Article
• Language: English
• Published: MDPI AG 2024-05-01
• Subjects: gold nanoparticles; docetaxel; radiotherapy; pancreatic cancer; in vivo
• Online Access: https://www.mdpi.com/1999-4923/16/6/713

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% (<i>p</i> = 0.05) decrease in spheroid size and a 45% (<i>p</i> = 0.05) increase in DNA DSBs. In vivo results showed a 20% (<i>p</i> = 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.