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Life sciences · Journal article
Frontiers in Pharmacology · October 9, 2026
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Introduction Breast cancer remains the most frequently diagnosed malignancy and the leading cause of cancer death among women worldwide as of 2026. While conventional interventions face challenges like drug resistance and systemic toxicity, the integration of green nanotechnology with ethnopharmacology offers a biocompatible, sustainable alternative. This review assesses the mechanistic pathways and therapeutic potential of phytogenic zinc oxide nanoparticles (ZnO NPs) synthesized using bioactive secondary metabolites. Methods This review combines findings from nine recent studies exploring biogenic ZnO NPs derived from diverse biological sources, including Rhus coriaria L. (Anacardiaceae), Withania somnifera (L.) Dunal (Solanaceae), Zingiber officinale Roscoe (Zingiberaceae). We critically analysed the characterization parameters, synthesis methods and pharmacological efficacy across 3D architectural spheroids, 2D monolayer cultures, and select in vivo models. Results The collective data demonstrate that biogenic ZnO-NPs induce potent apoptosis through BAX upregulation, ROS-mediated mitochondrial dysfunction and specific cell cycle arrest. Notable benchmarks include tumour suppression comparable to Tamoxifen in in vivo models using melon-derived extracts and an IC50 of 14.7 μg/mL in 3D MCF-7 spheroids for ginger-mediated NPs. Discussion In spite of the promising results, a critical methodological tension exists between limited preclinical validation and innovative synthesis. The pervasive reliance on 2D models often fails to duplicate the dense architectural barriers of solid tumours. Future research must prioritize a realistic translational pathway, shifting from basic in vitro models to rigorous in vivo biodistribution profiling, detailed metabolic tracking, and long-term toxicological assessments against normal mammary epithelial controls (e.g., MCF-10A) to actually establish, rather than merely hypothesize, a definitive, selective therapeutic index and ensure baseline physiological safety.