Urtica dioica Mediates Zinc-Copper Doped Nanoparticles as Potent Anticancer Agents against Human Breast Cancer MDA-MB-231 Cell Line.

Background: Recently, biosynthesis, also recognized as green synthesis, has emerged as an alternative for producing nano-metal oxides. In this study the anti-cancer activity of green-synthesized zinc-copper-doped NPs using Urtica dioica against the human BC-MDA-MB-231 cell line was investigated.

Materials and methods: The synthesized bimetallic NPs using U. dioica through Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM), coupled with energy-dispersive analysis of X-rays (EDX) and UV-Visible spectroscopy was characterized. MTT assay assessed the toxicity in BC cells induced by NP exposure, determining the lethal toxic dose. Additionally, apoptosis in cells resulting from NP exposure was evaluated using the real-time PCR technique. The potential mechanism of toxicity induced by doped NPs was further assessed by lactate dehydrogenase, caspase-3, and ROS generation in BC cells.

Results: The particles exhibited an irregular structure with non-uniform surfaces, and a variable size of NPs ranging between 22 and 46 nm was observed. Zn-doped-Cu NPs decreased the viability of MDA-MB-231 cells in both treatment groups in a dose-dependent manner. The IC₅₀ concentration of Zn-doped-Cu NPs significantly increased Bax expression and decreased Bcl2, MMP2, and MMP9 genes thus playing a crucial role in apoptosis and metastasis prevention. Furthermore, a notable increase in LDH activity, caspase-3 activity, and ROS generation was observed in cancerous cells following exposure to biosynthesized NPs compared to MDA-MB-231 cells receiving extract and the control group.

Conclusions: These findings underscore the remarkable apoptotic, antimetastatic, and antioxidant activity of biosynthesized Zn-doped-Cu NPs.