Head and neck cancer (HNC) is a genetically complex cancer type having treatment difficulties due to affecting multiple organs in complex anatomical sites. Radiotherapy resistance, chemotoxicity, post-surgery disability makes HNC treatment more complicated. Therefore, there is need to developed new treatment approaches. Nanoparticle-based therapies especially cerium oxide nanoparticles with its anti-cancer features, high catalytic activity, anti- or pro-oxidant and radio-protective properties give a boon for HNC treatment. In the current study, two dextran-coated cerium oxide nanoparticles (Dex-CeNPs) namely SD1 and SD2 were synthesized and characterized by using two types of dextran (D1 and D2) having distinct molecular weights and branching characteristics to understand their potential as a new HNC treatment strategy while evaluating the role of dextran type. The effectivity of the SD1 and SD2 on the HNC cell lines (A253, SCC-25, FaDu) were investigated by analyzing their cytotoxicity, genotoxicity, reactive oxygen species (ROS) generation properties. Low IC₅₀ value, high ROS generation and stability profiling of SD2 compared to SD1 indicates the distinct function of dextran type on Dex-CeNPs effectivity on HNC. To better elucidate the effectivity of SD2, flow cytometry analysis and pro-apoptotic (TP53, CASP3, BAX) and anti-apoptotic (Bcl-2) gene expression profiling were investigated in detail. The findings indicate that SD2 exhibits an influence on head and neck cancer cells via the apoptotic pathway. Our research sets the framework for the development of Dex-CeNPs as remarkable nanotherapeutic candidates for treatment of head and neck cancer.

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.