Combination of Conventional Chemotherapeutics with Redox-Active Cerium Oxide Nanoparticles—A Novel Aspect in Cancer Therapy

Abstract

Nanotechnology is becoming an important field of biomedical and clinical research and the application of nanoparticles in disease may offer promising advances in treatment of many diseases, especially cancer. Malignant melanoma is one of the most aggressive forms of cancer and its incidence is rapidly increasing. Redox-active cerium oxide nanoparticles (CNP) are known to exhibit significant antitumor activity in cells derived from human skin tumors in vitro and in vivo, whereas CNP is nontoxic and beyond that even protective (antioxidative) in normal, healthy cells of the skin. As the application of conventional chemotherapeutics is associated with harmful side effects on healthy cells and tissues, the clinical use is restricted. In this study, we addressed the question of whether CNP supplement a classical chemotherapy, thereby enhancing its efficiency without additional damage to normal cells. The anthracycline doxorubicin, one of the most effective cancer drugs, was chosen as reference for a classical chemotherapeutic agent in this study. Herein, we show that CNP enhance the antitumor activity of doxorubicin in human melanoma cells. Synergistic effects on cytotoxicity, reactive oxygen species generation, and oxidative damage in tumor cells were observed after co-incubation. In contrast to doxorubicin, CNP do not cause DNA damage and even protect human dermal fibroblasts from doxorubicin-induced cytotoxicity. A combination of classical chemotherapeutics with nongenotoxic but antitumor active CNP may provide a new strategy against cancer by improving therapeutic outcome and benefit for patients.

Toxicity and Protective Effects of Cerium Oxide Nanoparticles (Nanoceria) Depending on Their Preparation Method, Particle Size, Cell Type, and Exposure Route

“…Despite all the conflicting evidence on ceria toxicity, this material has very promising applications in areas such as drug delivery systems, [12] neurodegenerative disease therapy, [80] medical imaging, [81] and cancer treatment. [1,82] …”

Photosensitizer-Loaded Branched Polyethylenimine-PEGylated Ceria Nanoparticles for Imaging-Guided Synchronous Photochemotherapy

“…Other studies have demonstrated that heparin-nanoceria effectively decreases endothelial cell proliferation, suggesting the potential of CNPs for application in controlling cancer angiogenesis. 39 CNPs also enhance the anti-tumor activity of doxorubicin in human melanoma cells; 40 synergistic effects on cytotoxicity, ROS generation and oxidative damage were observed in tumor cells following co-incubation with CNPs and doxorubicin. The above findings demonstrate that CNPs exhibit selective cytotoxicity toward tumor cells.…”

Reprotoxicité des nanoparticules

“…Elle montre que l'injection intra-pé ritoné ale de NPs de dioxyde de cé rium a un effet antioxydant et antiangiogé nique. Ces mêmes effets pourraient jouer un rôle bé né fique dans les pathologies dé gé né ratives [24,25] et dans certains cancers [26][27][28][29]. Dans le domaine andrologique, l'é quipe de Chen a testé chez l'animal, un dispositif contraceptif composite intra-dé fé rentiel comprenant des nanoparticules de cuivre et de silice, permettant une obstruction efficace et ré versible, sans effet sur la spermatogenè se [30].…”