From trace element to therapeutic application: The emerging role of selenium nanoparticles in cancer therapy.

Selenium nanoparticles (SeNPs) are increasingly recognized as versatile therapeutic candidates in cancer treatment, owing to their distinctive and unique redox behavior, favorable biocompatibility, and tumor-selective cytotoxic effects. Compared with traditional Se compounds, SeNPs offer reduced toxicity and improved bioavailability, making them a reliable candidate for therapeutic applications. SeNPs have been synthesized through various approaches, including chemical and physical methods, as well as biosynthesis. Recent advances in SeNP biosynthesis using plant extracts and microorganisms, have improved sustainability and reproducibility. SeNPs demonstrated multiple biological mechanisms, including modulation of oxidative stress, epigenetic remodeling, immune signaling pathways, and programmed cell death, thereby contributing to tumor suppression and enhancing sensitivity to anticancer therapies. Additionally, their synergistic interactions with conventional chemotherapeutic agents enhance therapeutic outcomes, mitigate systemic toxicity, and help circumvent multidrug resistance. SeNPs interact with critical molecular regulators, including P-glycoprotein, caspase family proteases, and chromatin-modifying enzymes, thereby promoting apoptotic signaling and restoring the expression of epigenetically silenced tumor suppressor genes. In parallel, Se-based compounds regulate non-coding RNA networks and inflammation-associated signaling pathways, thereby promoting immune-mediated elimination of malignant cells. This review discusses recent evidence on SeNPs, spanning molecular mechanisms and translational applications, and emphasizes their multifunctional therapeutic potential and promise as redox-sensitive nanosystems in targeted therapeutic strategies.