Selenium-Tellurium Hybrid Nanoparticles: Selectivity, Mechanisms of Redox Modulation, and Therapeutic Prospects in Oncology.

Advances in nanotechnology over the past decade have led to breakthroughs in developing new antitumor agents, with nanoparticles being used both as independent therapeutic agents and as drug delivery systems. Although selenium nanoparticles (SeNPs) are relatively well-studied, the potential of tellurium nanoparticles (TeNPs) and their hybrid forms Se-TeNRs (Se-Te nanorods) remains largely unexplored. This work investigated the cytotoxic effects and molecular mechanisms of action of SeNPs, TeNPs, and Se-TeNRs on mouse testicular teratoma cells (F-9) and fibroblasts (L-929) revealing significant differences in their biological activity. Our experiments demonstrated that Se-TeNRs exhibited pronounced selectivity, eliminating 99% of tumor cells (F-9) at a concentration of 5 µg/mL through the induction of apoptosis, while maintaining the viability of normal fibroblasts (L-929). This selective cytotoxicity correlated with distinct patterns of redox modulation: in F-9 cancer cells, SeNPs and Se-TeNRs induced oxidative stress by activating NOX-family genes (up to 6.3-fold) and suppressing antioxidant genes (SOD1, CAT, HO-1 by 2-3.8 times). In contrast, in normal L-929 fibroblasts, the same particles exerted an antioxidant effect, increasing the expression of antioxidant genes (SOD1, CAT, HO-1 by 1.7–3.7 times) while suppressing pro-oxidant enzymes (NOX1-4). TeNPs showed intermediate effects with dose-dependent induction of apoptosis (EC₅₀ = 2.9 µg/mL in L-929 vs. 6.2 µg/mL in F-9). Calcium signaling studies revealed that TeNPs induced rapid Ca²⁺ transients (EC₅₀ = 2.9 µg/mL in L-929), whereas Se-TeNRs led to sustained depletion of Ca²⁺ stores specifically in tumor cells, triggering apoptosis. Migration analysis further confirmed the therapeutic potential of Se-TeNRs, which completely suppressed F-9 cell migration at concentrations of 1 µg/mL and above, without affecting wound healing in L-929. The obtained data suggest that Se-TeNRs exert their antitumor effects through coordinated modulation of redox status and disruption of calcium signaling, offering a promising platform for targeted cancer therapy with reduced side effects. The differential response of normal and tumor cells to these nanoparticles highlights their potential as precision therapeutic agents in oncology.