Selenium nanoparticles for breast cancer: mechanisms, delivery strategies, and translational challenges

Breast cancer treatment remains limited by drug resistance, toxicity, and inadequate selectivity in aggressive subtypes, prompting continued interest in selenium-based agents whose anticancer activity depends strongly on chemical form, redox behavior, and metabolic fate. This review critically compares inorganic, organic, and nanoscale selenium, with particular emphasis on selenium nanoparticles (SeNPs) as engineerable platforms for breast cancer therapy. Current evidence indicates that selenium-based agents primarily exert antitumor effects through disruption of redox homeostasis, induction of apoptosis, and modulation of survival signaling pathways such as PI3K/AKT/mTOR, while additional effects on autophagy, metastasis, angiogenesis, and treatment resistance appear to be more context-dependent. Compared with conventional selenium compounds, SeNPs offer greater formulation flexibility through surface modification, cargo loading, and stimulus-responsive design, and have shown promising activity especially in triple-negative and HER2-positive breast cancer models. However, clinical translation is restricted by the lack of breast cancer-specific early-phase therapeutic studies and by persistent uncertainties regarding the therapeutic window, pharmacokinetics, long-term safety, manufacturing reproducibility, and patient selection. By integrating selenium speciation, SeNP preparation strategies, subtype-oriented applications, and translational barriers, this review highlights that future progress will depend on standardized formulations, rigorous in vivo validation, and biomarker-informed clinical development rather than unselected selenium use.