Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells

Abstract

Jessica Swanner,1 Jade Mims,2 David L Carroll,3,4 Steven A Akman,5 Cristina M Furdui,2 Suzy V Torti,6 Ravi N Singh1,7 1Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, NC, USA; 2Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA; 3Center for Nanoscale and Molecular Materials, Wake Forest University, Winston-Salem, NC, USA; 4Department of Physics, Wake Forest University, Winston-Salem, NC, USA; 5Roper St Francis Cancer Care, Charleston, SC, USA; 6Department of Molecular Biology and Biophysics, University of Connecticut Health Center, CT, USA; 7Comprehensive Cancer Center of Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Identification of differential sensitivity of cancer cells as compared to normal cells has the potential to reveal a therapeutic window for the use of silver nanoparticles (AgNPs) as a therapeutic agent for cancer therapy. Exposure to AgNPs is known to cause dose-dependent toxicities, including induction of oxidative stress and DNA damage, which can lead to cell death. Triple-negative breast cancer (TNBC) subtypes are more vulnerable to agents that cause oxidative stress and DNA damage than are other breast cancer subtypes. We hypothesized that TNBC may be susceptible to AgNP cytotoxicity, a potential vulnerability that could be exploited for the development of new therapeutic agents. We show that AgNPs are highly cytotoxic toward TNBC cells at doses that have little effect on nontumorigenic breast cells or cells derived from liver, kidney, and monocyte lineages. AgNPs induced more DNA and oxidative damage in TNBC cells than in other breast cells. In vitro and in vivo studies showed that AgNPs reduce TNBC growth and improve radiation therapy. These studies show that unmodified AgNPs act as a self-therapeutic agent with a combination of selective cytotoxicity and radiation dose-enhancement effects in TNBC at doses that are nontoxic to noncancerous breast and other cells. Keywords: DNA damage, radiation sensitizer, glutathione, redox