title: The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments.
abstract: Angiogenesis is the formation of new blood vessels from existing blood vessels and is critical for many physiological and pathophysiological processes. In this study we have shown the unique property of cerium oxide nanoparticles (CNPs) to induce angiogenesis, observed using both in vitro and in vivo model systems. In particular, CNPs trigger angiogenesis by modulating the intracellular oxygen environment and stabilizing hypoxia inducing factor 1α endogenously. Furthermore, correlations between angiogenesis induction and CNPs physicochemical properties including: surface Ce(3+)/Ce(4+) ratio, surface charge, size, and shape were also explored. High surface area and increased Ce(3+)/Ce(4+) ratio make CNPs more catalytically active towards regulating intracellular oxygen, which in turn led to more robust induction of angiogenesis. Atomistic simulation was also used, in partnership with in vitro and in vivo experimentation, to reveal that the surface reactivity of CNPs and facile oxygen transport promotes pro-angiogenesis.
authors.affiliation: Department of Mechanical, Materials and Aerospace Engineering, University of Central Florida, Orlando, FL 32816, USA.
authors.forename: Soumen
authors.initials: S
authors.lastname: Das
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
authors.forename: Janet M
authors.initials: JM
authors.lastname: Dowding
authors.forename: Saji
authors.initials: S
authors.lastname: Oommen
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Thi X T
authors.initials: TX
authors.lastname: Sayle
authors.forename: Shashank
authors.initials: S
authors.lastname: Saraf
authors.forename: Chitta R
authors.initials: CR
authors.lastname: Patra
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Vlahakis
authors.forename: Dean C
authors.initials: DC
authors.lastname: Sayle
authors.forename: William T
authors.initials: WT
authors.lastname: Self
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000187:drug effects*; D002563:Cerium / Q000494:pharmacology*; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D010316:Particle Size; D055672:Static Electricity; D013499:Surface Properties / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D002563:Cerium; C030583:ceric oxide; D010100:Oxygen