The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments

    Authors

    S. Das; S. Singh; J. M. Dowding; S. Oommen; A. Kumar; T. X. T. Sayle; S. Saraf; C. R. Patra; N. E. Vlahakis; D. C. Sayle; W. T. Self;S. Seal

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    Abbreviated Journal Title

    Biomaterials

    Keywords

    Cerium oxide nanoparticle; Angiogenesis; Hypoxia inducing factor 1; alpha; Intracellular oxygen concentration; Molecular dynamics; Surface; reactivity; ENDOTHELIAL GROWTH-FACTOR; CELL-PROLIFERATION; TUMOR HYPOXIA; DYSFUNCTION; VACANCIES; SURFACES; NANORODS; Engineering, Biomedical; Materials Science, Biomaterials

    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 1 alpha endogenously. Furthermore, correlations between angiogenesis induction and CNPs physicochemical properties including: surface Ce3+/Ce4+ ratio, surface charge, size, and shape were also explored. High surface area and increased Ce3+/Ce4+ 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. (c) 2012 Elsevier Ltd. All rights reserved.

    Journal Title

    Biomaterials

    Volume

    33

    Issue/Number

    31

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    7746

    Last Page

    7755

    WOS Identifier

    WOS:000308619000008

    ISSN

    0142-9612

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