Anti-angiogenic activity of heparin functionalised cerium oxide nanoparticles

• Published in: Biomaterials Vol. 34; no. 34; pp. 8808 - 8818
• Main Authors: Lord, Megan S, Tsoi, Bonny, Gunawan, Cindy, Teoh, Wey Yang, Amal, Rose, Whitelock, John M
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2013
• Subjects: Advanced Basic Science; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival; Cerium - chemistry; Cerium - pharmacology; Cerium oxide; Dentistry; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Heparin; Heparin - pharmacology; Humans; Lysosomes - drug effects; Lysosomes - metabolism; Nanoparticle; Nanoparticles - chemistry; Neovascularization, Pathologic - drug therapy; Propylamines; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction; Silanes - chemistry; Angiogenesis; Reactive oxygen species; Heparin; Cerium oxide; Nanoparticle; Endothelial cells
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.07.083

Abstract Cerium oxide nanoparticles (nanoceria) are widely reported to be non-cytotoxic and modulate intracellular reactive oxygen species (ROS). In this study, nanoceria ( dxRD  = 12 nm) were functionalised with either 130 or 880 molecules of unfractionated heparin using the organosilane linker, 3-aminopropyltriethoxysilane. Nanoceria with a low level of heparin functionalisation were found to scavenge intracellular ROS to the same extent as unfunctionalised nanoceria and significantly more than cells exposed to medium only. In contrast, nanoceria with the highest level of heparin functionalisation were not as effective at scavenging intracellular ROS. Nanoceria were localised predominantly in the cytoplasm, while heparin-nanoceria were localised in both the cytoplasm and lysosomes. Together these data demonstrated that the level of nanoceria surface functionalisation with heparin determined the intracellular localisation and ROS scavenging ability of these particles. Additionally, heparin-nanoceria were effective in reducing endothelial cell proliferation indicating that they may find application in the control of angiogenesis in cancer in the future.