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

Abstract

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 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 non-cancerous 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 one 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.

Cerium oxide nanoparticles: green synthesis and biological applications

“…Dextran was also used for CeO 2 -NP stabilizing and coating, as it is a biocompatible, complex and highly watersoluble polysaccharide. 57 Accordingly, NPs as small as 5 nm were produced which were toxic to cancer cells at pH 6 and much less toxic to normal cells at the same pH value. 57 Moreover, the importance and versatility of polyethylene glycol (PEG) for the functionalization of rare earth cerium oxide NPs were also investigated.…”

“…57 Accordingly, NPs as small as 5 nm were produced which were toxic to cancer cells at pH 6 and much less toxic to normal cells at the same pH value. 57 Moreover, the importance and versatility of polyethylene glycol (PEG) for the functionalization of rare earth cerium oxide NPs were also investigated. [58][59][60] The suggested mechanism for PEG-mediated ceria synthesis was the presence of an electrostatic driving force for the complexation.…”

Hot Topics and Challenges of Regenerative Nanoceria in Application of Antioxidant Therapy

“…Tarnuzzer's group found that nanoceria exhibited radioprotection of normal human breast epithelial cells, but not to MCF-7 cancer cells for the first time [24]. In addition, the size, shape, agglomeration state, surface charge, and surface modification of nanoceria together determine its bioresponse to cancer cells [41][42][43][44]. Dextran-coated nanoceria prepared by Alili et al [45] has been used to prevent myofibroblast formation and tumor invasion in tumor-stroma interaction.…”

Nanoparticles in biomedical applications

“…This has led to an increased interest in nanoceria as a potential biological antioxidant. Nanoceria has been used in biomedical applications as a biosensor and as an anticancer agent [191][192][193][194][195]. The use of porous silica (SiO 2 ) nanoparticles in biomedical applications is increasing due to its unique properties including large specific surface area, pore volume, controllable particle size and good biocompatibility.…”