Journal
BIOMATERIALS
Volume 33, Issue 31, Pages 7746-7755Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.07.019
Keywords
Cerium oxide nanoparticle; Angiogenesis; Hypoxia inducing factor 1 alpha; Intracellular oxygen concentration; Molecular dynamics; Surface reactivity
Funding
- NIH [1R01AG031529-01]
- NSF [0708172 CBET, 080473355 CBET]
- S.S. EPSRC [EP/H00122011]
- EPSRC [EP/H001220/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/H001220/1] Funding Source: researchfish
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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.
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