Anticancer Activity of a Novel Epoxyazadiradione AuNP Complex in TNBC Cells

Triple-negative breast cancer (TNBC) has attracted considerable global research interest due to its complex and poorly understood biology and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).

Therefore, identifying effective targeted therapeutic approaches for these cells remains a critical challenge. The role of phytochemicals in cancer prevention and treatment is well established and extensively documented. Additionally, gold nanoparticles (AuNPs) effectively address several limitations associated with phytochemicals. Therefore, the present study utilized the phytochemical epoxyazadiradione (EAZD) to reduce gold chloride to AuNPs, thereby forming the EAZD-AuNP complex. These AuNPs, ranging from 10-50 nm in size, can passively target tumor tissue via the enhanced permeability and retention (EPR) effect. Furthermore, the protein corona adsorbed onto the AuNPs facilitates cellular uptake via receptor-mediated endocytosis.

UV-visible spectroscopy, XRD, EDX, and TEM confirmed the formation of EAZD-AuNPs. Additionally, FTIR analysis confirmed the involvement of the carbonyl group of EAZD in the bioreduction of gold chloride. Moreover, in vitro studies using the MTT and colony formation assays revealed an antiproliferative effect of EAZD-AuNPs in TNBC cells, with an IC₅₀ value of 6 µg/mL. Furthermore, PI-FACS and live/dead assays confirmed that EAZD-AuNPs induced a greater extent of cell death than EAZD alone. Western blot analysis further demonstrated that EAZD-AuNPs trigger apoptosis through the regulation of cleaved caspase-3 and caspase-9 expression.

These findings substantiate the anticancer activity of the novel EAZD-AuNP complex. However, additional in vitro and in vivo studies are necessary to further validate its therapeutic potential and should be prioritized.