Green Synthesis of Gold Nanoparticles and Study of Their Inhibitory Effect on Bulk Cancer Cells and Cancer Stem Cells in Breast Carcinoma

Abstract

Chemo-resistance from cancer stem cells (CSCs) subpopulation is a current issue in cancer treatment. It is important to select alternative therapies to efficiently eradicate both bulk cancer cells and CSCs. Here, gold nanoparticles (AuNPs) have been selected regarding their biocompatibility, facile and controllable synthesis, potent anti-cancer activity and photothermal conversion performance. We reported a green synthesis of functionalized AuNPs using hyaluronic acid (HA) as a reductant, capping, stabilizing and hydrophilic substance. The resultant AuNPs were spherical-shaped with an average diameter of around 30 nm. These AuNPs displayed improved physico-chemical (yield, stability, photothermal effect) and biological properties (cellular uptake, cytotoxicity and apoptotic effect) against bulk MDA-MB-231 cells, in comparison with other organic anti-cancer drugs. The intensified bioactivity was dependent on a mitochondria-mediated cascade, reflected by the damage in mitochondria, oxidative stress, intensified Caspase 3 activity and increased/decreased expression of certain pro-apoptotic (Bax, P53, Caspase 3)/anti-apoptotic (Bcl-2) genes. Moreover, these AuNPs posed a dramatically improved inhibitory effect in cell viability and self-renewable capacity on CSC subpopulation. All the results were attributed from the nano-scaled structure of AuNPs and combined effect from NIR-induced hyperthermia. In addition, the biocompatible nature of these AuNPs supported them to be a potential candidate in the development of novel chemotherapeutic drugs.