Anti-angiogenic activity of heparin functionalised cerium oxide nanoparticles

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-...

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Bibliographic Details
Published in:Biomaterials 2013-11, Vol.34 (34), p.8808-8818
Main Authors: Lord, Megan S, Tsoi, Bonny, Gunawan, Cindy, Teoh, Wey Yang, Amal, Rose, Whitelock, John M
Format: Article
Language:English
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
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.07.083