Secret elixirs of nature: extract type shapes the phytochemical-mediated synthesis and anticancer potential of ZnO and Fe₂O₃ nanoparticles from Salvadora persica

Recently, the field of phyto-nanomedicines has emerged as a promising avenue of research for generating sustainable, economically viable, and medically safe plant-based metal nanoparticles (NPs) with boosted therapeutic potential. Despite advancements, the literature remains inconclusive regarding the optimal extraction protocol for these plants to yield NPs with maximized functionality. Therefore, this study pioneered the use of two diverse UAE-Salvadora persica extracts; namely, aqueous and hydro-alcoholic, in the biological synthesis of green zinc and iron oxides NPs, aiming to resolve the research gap concerning the ideal extraction protocol for biomedical green NPs’ production. Our findings revealed that the alcoholic extract yielded NPs with superior phytochemical surface coating, and higher phenolic (42.94 ± 2.79 µg of GAE/mg of DW) and flavonoid (45.63 ± 1.88 µg of QU/mg of DW) contents, resulting in stronger antioxidant properties with IC_50s ranging from 69.68 µg/mL to 180.26 µg/mL. Nevertheless, the aqueous extract demonstrated superior reducing efficacy, and its corresponding zinc oxide NPs exhibited the strongest cytotoxicity against A-431 cells (IC₅₀:377.39 µg/mL), surpassing the activity of its parent crude extract. These extract-dependent nanoparticle variations were further confirmed and resonated via QTOF-LC/MS/MS and Principal Component Analysis analyses. Thus, our findings emphasize that selection of appropriate extraction protocols is crucial for therapeutic plant-based NPs’ development.