Flower-shaped ZnO nanoparticles from Lactococcus lactis LAB2: potential selective anti-cancer activity via oxidative...

Biosynthesized zinc oxide nanoparticles (ZnO-NP2) produced using Lactococcus lactis culture supernatant demonstrate exceptional selectivity as anticancer agents. These flower-like nanoparticles maintained 96.44% viability in normal HUVEC cells, while reducing the viability of HCT116 and K562 cancer cells to 58.92% and 39.24%, respectively, at a concentration of 0.25 mg/mL. Acridine orange-ethidium bromide staining confirmed dose-dependent apoptosis induction, with K562 cells exhibiting a combined apoptotic and necrotic population of 61.66%. Oxidative stress analysis revealed sophisticated cell-type-specific redox modulation, including a 46.9% upregulation of catalase compared to the control in HCT116 cells, elevated lipid peroxidation, and increased levels of nitric oxide and glutathione. Gene expression analysis revealed dramatic alterations in the apoptotic pathway: HCT116 cells exhibited a 29.68-fold upregulation of BAX, while K562 cells demonstrated a 0.05-fold downregulation of BCL2. Physicochemical characterization confirmed successful synthesis with protein coating (evidenced by FTIR peak at 1635.95 cm⁻¹), negative surface charge (-25 to -30 mV), and crystalline flower-like morphology. Paradoxically, ZnO-NP2 showed antioxidant activity in cell-free DPPH assays (63.15% reduction) despite pro-oxidant effects in cancer cells. ZnO-NP2 induced selective cancer cell apoptosis through modulation of oxidative stress and activation of the intrinsic apoptotic pathway in vitro, suggesting preliminary potential for development as targeted anticancer agents, pending comprehensive in vivo validation and mechanistic studies.