Repurposing antimalarial pyronaridine as a DNA repair inhibitor to exploit the full potential of gold-nanoparticle-mediated radiation response
Date
2022
Authors
Jackson, Nolan
Alhussan, Abdulaziz
Bromma, Kyle
Jay, David
Donnelly, James C.
West, Frederick G.
Lavasanifar, Afsaneh
Weinfeld, Michael
Beckham, Wayne
Chithrani, Devika B.
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmaceutics
Abstract
Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in
RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control
in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold
nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The
objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as
a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We
were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results
show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with
PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore,
there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated
cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel
concepts introduced in this study could lay the foundation for the transition of this treatment modality
into clinical environments.
Description
Keywords
gold nanoparticles, pyronaridine, cancer cells, radiotherapy, DNA repair, ERCC1-XPF, nanomedicine
Citation
Jackson, N., Alhussan, A., Bromma, K., Jay, D., Donnelly, J. C., West, F. G., . . . Chithrani, D. B. (2022). “Repurposing antimalarial pyronaridine as a DNA repair inhibitor to exploit the full potential of gold-nanoparticle-mediated radiation response.” Pharmaceutics, 14(12), 2795. https://doi.org/10.3390/pharmaceutics14122795