Cerium Oxide Nanoparticles as a Novel Nanodrug

• Main Author: Alpaslan, Ece
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2017
• Subjects: Bioengineering; Chemical engineering; Materials science
• ISBN: 0355235803; 9780355235807

Cerium oxide nanoparticles (nanoceria) have been shown to effectively modulate reactive oxygen species (ROS) levels within cells due to its unique physiochemical structure. In ceria oxides, both oxidation states (III) and (IV) can coexist, producing a redox couple that is responsible for ceria’s catalytic activity. The central focus of this thesis is to engineer nanoceria to induce ROS generation in vitro to fight severe diseases such as cancer, inflammation, and infection. ROS are considered oncogenic, as they are present at elevated amounts in cancer cells and they contribute to the initiation, progression and metastasis of cancer. However, in non-surgical cancer treatment approaches, such as radiotherapy, ROS generation within cancer cells is a common way to target cancer cells. For the first project, we engineered sub 5 nm nanoceria (+4) to effectively kill the cancer cells at different pH values, resembling the cancerous and non-cancerous environment. We found that dextran-coated nanoceria were much more efficient at killing bone cancer cells (osteosarcoma cells) in a slightly acidic environment (pH 6), compared to physiological and basic pH values (pH 7 and pH 9). In contrast to the cancer cells, approximately 2–3 fold higher healthy bone cell viabilities were observed compared to osteosarcoma cell viabilities when cultured with nanoceria at pH 6. Moreover, osteosarcoma cells showed elevated ROS generation under these conditions, whereas healthy osteoblast cells did not have show significant increases after 1 day treatment. Secondly, the antibacterial activity of nanoceria (+4) was examined against Pseudomonas aeruginosa and Staphylococcus epidermidis by varying the nanoparticle concentration and the pH of the solution. Findings suggested that nanoceria particles were much more effective at killing P. aeruginosa and S. epidermidis at basic pH values (pH = 9) compared to acidic pH values (pH = 6). For both bacteria, a 2 log reduction and elevated amounts of ROS generation per colony were observed and P. aeruginosa showed drastic morphological changes as a result of cellular stress after 6 hours of treatment (with nanoceria at pH 9) compared to untreated controls. Overall, ROS are detrimental by-products of cellular systems, and it has been shown that oxidative stress is linked with cancer and infection. In this study, we engineered cerium oxide nanoparticles to generate ROS to selectively kill the cancer cells and inhibit bacterial infection by controlling the pH of the solution.