title: Cellular uptake and activity of heparin functionalised cerium oxide nanoparticles in monocytes.
abstract: Cerium oxide nanoparticles (nanoceria) are effective in scavenging intracellular reactive oxygen species (ROS). In this study nanoceria synthesized by flame spray pyrolysis (dXRD = 12 nm) were functionalised with heparin via an organosilane linker, 3-aminopropyltriethoxysilane. Nanoceria were functionalised with approximately 130 heparin molecules per nanoparticle as determined by thermo gravimetric analysis. Heparin functionalised nanoceria were more effectively internalised by the human monocyte cell line, U937, and U937 cells that had been activated with phorbol 12 myristate 13-acetate (PMA) than bare nanoceria. The heparin functionalised nanoceria were also more effective in scavenging ROS than nanoceria in both activated and unactivated U937 cells. Heparin coupled nanoceria were found to be biologically active due to their ability to bind fibroblast growth factor 2 and signal through FGF receptor 1. Additionally, the heparin-coupled nanoceria, once internalised by the cells, were found to be degraded by 48 h. Together these data demonstrated that heparin enhanced the biological properties of nanoceria in terms of cellular uptake and ROS scavenging, while the nanoceria themselves were more effective at delivering heparin intracellularly than exposing cells to heparin in solution.
authors.affiliation: Graduate School of Biomedical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: S R Simon
authors.initials: SR
authors.lastname: Ting
authors.forename: John M
authors.initials: JM
authors.lastname: Whitelock
authors.forename: Romana
authors.initials: R
authors.lastname: Tomic
authors.forename: Cindy
authors.initials: C
authors.lastname: Gunawan
authors.forename: Wey Yang
authors.initials: WY
authors.lastname: Teoh
authors.forename: Rose
authors.initials: R
authors.lastname: Amal
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lord
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002563:Cerium / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D004705:Endocytosis / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005434:Flow Cytometry; D006493:Heparin / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010084:Oxidation-Reduction / Q000187:drug effects; D011437:Propylamines; D011485:Protein Binding / Q000187:drug effects; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012821:Silanes / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D020298:U937 Cells
chemical_list: D011437:Propylamines; D012821:Silanes; D016222:Fibroblast Growth Factor 2; D002563:Cerium; C030583:ceric oxide; D006493:Heparin; D051496:Receptor, Fibroblast Growth Factor, Type 1; C477625:amino-propyl-triethoxysilane