Tellurium nanoparticles produced by laser ablation induce selective anticancer effects via ROS-mediated apoptosis and calcium signaling pathways: In vitro screening.

Over the past decade, increasing attention has been directed toward the development and evaluation of novel anticancer agents based on nanotechnology. Nanoparticles (NPs) have emerged both as standalone anticancer agents and as carriers for targeted drug delivery. Various types of nanoparticles are being investigated in combinatorial cancer therapies alongside radiotherapy or immunomodulatory agents, with the aim of reducing drug resistance and enhancing apoptotic responses within tumors. Despite this progress, the potential of tellurium nanoparticles (TeNPs) as anticancer agents remains largely unexplored. Current studies on nanostructured tellurium are often fragmented, and mechanistic hypotheses are frequently extrapolated from those of selenium-based nanoparticles. In the present study, we investigated the anticancer properties of TeNPs of two distinct diameters - small (∼10 nm) and larger (∼100 nm) - using a comprehensive in vitro approach. We conducted experiments on four human cancer cell lines: glioblastoma (A-172), hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF-7), and neuroblastoma (SH-SY5Y), along with a mouse fibroblast cell line (L-929) as a non-cancerous control. Fluorescence microscopy was employed to monitor intracellular calcium dynamics and reactive oxygen species (ROS) production. Additional assays included apoptotic and necrotic cell death tests and quantitative polymerase chain reaction (PCR) to analyze gene expression profiles. Our screening revealed that TeNPs exhibit anticancer activity, though not uniformly across all tested cancer cell lines. TeNPs induced apoptosis in all cancer cell types without triggering necrosis, albeit with varying efficacy. These differences correlated with cell line-specific expression levels of pro-apoptotic genes. Differential effects on cellular redox status and ROS production further accounted for the observed variability in TeNPs anticancer effects. Both sizes of TeNPs significantly inhibited cell migration in MCF-7 and HepG2 cells across a broad concentration range. In contrast, migration was unaffected in A-172 and SH-SY5Y cells. Notably, TeNPs also reduced the motility of L-929 fibroblasts, but only after 48 h of exposure. We further demonstrate that TeNPs activate calcium signaling pathways in a dose-dependent manner in both cancerous and non-cancerous cells. However, the effective concentration (EC50, half-maximal effective concentration) and the amplitude and morphology of calcium responses varied considerably between cell types. Collectively, our findings highlight the promising but selective anticancer potential of TeNPs, suggesting their effects are mediated through redox modulation and calcium-dependent signaling pathways. These results provide a basis for the further development of tellurium-based nanomaterials in cancer therapeutics.