Aptamer-Functionalized Redox-Responsive Mesoporous Organosilica-Coated Selenium Nanoparticles for Targeted Therapy of Triple-Negative Breast Cancer Cells

Selenium nanoparticles (SeNPs) exhibit tumor-suppressive capabilities via reactive oxygen species (ROS)-mediated mitochondrial dysfunction, yet their biomedical application remains constrained by poor targeting specificity and aqueous instability. Herein, we engineered glutathione-responsive therapeutic nanoparticles by encapsulating SeNPs within mesoporous organosilica (MON) isolation layers to ensure aqueous stability, while conjugating LXL-1 aptamers for targeted delivery to triple-negative MDA-MB-231 breast cancer cells. In vitro assessments across breast cell lines (MDA-MB-231 vs MCF-10A/MCF-7) revealed a 5.32-fold increase in cellular uptake of functionalized SeNPs in target cells, attributed to aptamer-mediated recognition. The optimized nanoformulation exhibited potent cytotoxicity comparable to doxorubicin-loaded MON controls at equivalent doses. Moreover, the aptamer-functionalized system significantly reduced cancer cell survival compared to the unmodified group (IC₅₀ = 161.2 μg/mL vs 71.13 μg/mL). This dual-functional nanoplatform not only enhances tumor-specific accumulation of SeNPs but also establishes a chemotherapy-alternative strategy with minimized systemic toxicity, advancing the development of selenium-based targeted nanomedicines.