Current standard treatments for osteosarcoma have not been changed for decades and have limited and variable success. The advancement of precision medicine technologies, along with the drug-repurposing and fast drug-screening methodologies available, has opened new avenues for the development of more effective therapeutic strategies. In this study, we evaluated the effectiveness of halogenated boroxine (HB) and dextran-coated cerium oxide nanoparticles—DexCeNPs (SD2)—in an in vitro osteosarcoma model. Both agents were tested individually and in combination. The research encompassed assessments of treatment-related cytotoxicity and cell viability, oxidative stress, and apoptotic and necrotic responses, as well as the effects on 3D spheroid models. The results demonstrated that the effects of HB and SD2 were strongly influenced by the dose, exposure time, and cell type. Both exhibited distinguished antitumor activity through cytotoxicity and specific reactive oxygen species (ROS) induction. The combined treatment produced modulated responses that were dependent on the treatment ratio and cell line, suggesting potential synergistic or selective interactions. Notably, the outcomes of the analysis conducted in 3D models revealed reduced toxicity toward non-tumor cells. These findings suggest the improved efficacy of HB and SD2 used in combination as a selective and novel antitumor strategy and underscore the need for further mechanistic studies at the transcriptomic and proteomic levels to elucidate the underlying pathways and clarify the mechanisms of action.

Colorectal cancer (CRC) remains a major cause of cancer death, and advanced disease is still limited by resistance and systemic toxicity. We studied intrinsically active, biomimetic cerium oxide nanoparticles (CeNPs) functionalized with D- or L-cysteine (D-Cys@CeNPs and L-Cys@CeNPs) in three CRC cell lines (COLO-201, DLD-1, and LoVo) and healthy colon fibroblasts (CCD-18Co). We propose these materials act as enantioselective functional keys: cysteine stereochemistry shapes recognition at the nano–bio interface, while productive interactions allow the Ce³⁺-rich surface to drive localized redox exchange. We measured viability, ROS as a downstream phenotypic readout, Annexin V/PI-defined cell fate, and expression of the NF-κB regulatory genes TNFAIP3 (A20), IKBKG (NEMO), and NFKBIA (IκBα). Across the CRC panel, D-Cys@CeNPs caused earlier and stronger loss of viability, with the clearest effect in COLO-201, and shifted cells toward late apoptosis and necrosis. In contrast, L-Cys@CeNPs produced slower and more heterogeneous fate changes. Gene expression showed enantiomer-dependent differences in NF-κB feedback, consistent with differential pathway engagement. CCD-18Co fibroblasts were comparatively resistant to both enantiomers. Together, these findings link chiral CeNP surface design to redox-linked pathway regulation and support a materials-based route to selective anticancer activity. INTRODUCTION