Antitumor efficacy of synthesized Ag–Au nanocomposite loaded with PEG and ascorbic acid in human lung cancer stem cells

Abstract

Lung cancer is the leading cause of mortality worldwide of which non-small cell lung carcinoma constitutes majority of the cases. High mortality is attributed to early metastasis, late diagnosis, ineffective treatment and tumor relapse. Chemotherapy and radiotherapy form the mainstay of its treatment. However, their associated side effects involving kidneys, nervous system, gastrointestinal tract, and liver further adds to dismal outcome. These disadvantages of conventional treatment can be circumvented by use of engineered nanoparticles for improved effectiveness with minimal side effects.In this study we have synthesized silver gold nanocomposite (Ag–Au NC) using polyethylene glycol and l-ascorbic acid as surfactant and reducing agent respectively. Synthesized nanocomposite was characterized by ultraviolet–visible absorption, dynamic light scattering, scanning and transmission electron microscopy. Compositional analysis was carried out by energy dispersive X-ray analysis and average pore diameter was estimated using Barrett-Joyner-Halenda method. In-silico molecular docking analysis of the synthesized NC against active regions of epidermal growth factor receptor revealed good binding energy. Subsequently, we investigated the effect of NC on growth and stem cell attributes of A549 lung cancer cells. Results showed that NC was effective in inhibiting A549 cell proliferation, induced DNA damage, G2/M phase arrest and apoptosis. Further, tumor cell migration and spheroid formation were also negatively affected. NC also enhanced reactive oxygen species generation and mitochondrial depolarization. In addition, the effect of NC on putative cancer stem cells in A549 cells was evaluated. We found that Ag–Au NC at IC50 targeted CD44, CD24, CD166, CD133 and CD326 positive cancer stem cells and induced apoptosis. CD166 positive cells were relatively resistance to apoptosis.Together our results demonstrate the anticancer efficacy of Ag–Au NC mediated by a mechanism involving cell cycle arrest and mitochondrial derangement.