Co3O4 Nanoparticles Synthesized With Urtica dioica Extract Versus Chemical Reduction: Enhanced ROS Generation, Cytotoxicity, and Cancer‐Cell Selectivity

Abstract

Cobalt oxide (Co3O4) nanoparticles are redox-active metal oxides with promising anticancer activity, but whether Urtica dioica extract-mediated synthesis improves their performance relative to conventional chemical synthesis remains unclear. In this study, bare Co3O4 nanoparticles were prepared by chemical reduction and Urtica dioica extract-synthesized nanoparticles (UD-Co3O4) were prepared by green synthesis in which the extract constituted the reaction medium, and the two formulations were compared. Energy-dispersive X-ray spectroscopy and infrared spectroscopy confirmed an Urtica dioica-derived organic coating on UD-Co3O4, which increased the hydrodynamic size (108.0 ⟶ 169.9 nm) and reduced the magnitude of the surface charge (-27.23 ⟶ -18.19 mV). Cytotoxicity was evaluated against A549, MDA-MB-231 and SH-SY5Y cancer cells and nontumorigenic L929 fibroblasts, with parallel measurement of intracellular reactive oxygen species (ROS). UD-Co3O4 was several-fold more cytotoxic than the bare Co3O4 against all cancer lines, with IC50 values of 29.4, 55.1 and 62.6 μg mL-1 versus 320.7, 307.1 and > 1000 μg mL-1, respectively, corresponding to an approximately 5- to > 15-fold increase in potency. UD-Co3O4 also generated higher ROS (for example, 324% vs. 279% of control in A549 at 1000 μg mL-1). Crucially, UD-Co3O4 showed cancer selectivity (selectivity index of 1.94 in A549 and 1.04 in MDA-MB-231) that the bare Co3O4 lacked (SI ≤ 0.28). ROS was the strongest predictor of viability in random-forest analysis (relative importance 0.58), and analysis of covariance indicated significantly greater cytotoxicity per unit of oxidative stress in cancer cells (pooled p = 0.007). Urtica dioica extract synthesis therefore enhances both the potency and the cancer selectivity of Co3O4 nanoparticles, consistent with a ROS-mediated mechanism.

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