pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Prohibiting Osteosarcoma Cell Proliferation

Cerium oxide nanoparticles (or nanoceria) have demonstrated great potential as antioxidants in various cell culture models. Despite such promise for reducing reactive oxygen species and an ability for surface functionalization, nanoceria has not been extensively studied for cancer applications to date. Herein, we engineered the surface of nanoceria with dextran and observed its activity in the presence bone cancer cells (osteosarcoma cells) at different pH values resembling the cancerous and noncancerous environment. We found that dextran coated nanoceria was much more effective at killing bone cancer cells at slightly acidic (pH 6) compared to physiological and basic pH values (pH 7 and pH 9). In contrast, minimal toxicity was observed for healthy (noncancerous) bone cells when cultured with nanoceria at pH = 6 after 1 day of treatment in the concentration range of 10-1000 μg/mL. Although healthy bone cancer cell viability decreased after treatment with high ceria nanoparticle concentrations (250-1000 μg/mL) for longer time periods at pH 6 (3 days and 5 days), approximately 2-3 fold higher healthy bone cell viabilities were observed compared to osteosarcoma cell viability at similar conditions. Very low toxicity was observed for healthy osteoblasts cultured with nanoceria for any concentration at any time period at pH 7. In this manner, this study provides the first evidence that nanoceria can be a promising nanoparticle for treating bone cancer without adversely affecting healthy bone cells and thus deserves further investigation.