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

Department of Mechanical, Materials and Aerospace Engineering, University of Central Florida, Orlando, FL 32816, USA.
Biomaterials (Impact Factor: 8.56). 08/2012; 33(31):7746-55. DOI: 10.1016/j.biomaterials.2012.07.019
Source: PubMed


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.

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    • "The large set of toxicological studies on nCeO 2 demonstrated the ability of nCeO 2 to act as a reactive oxygen species (ROS) regulator depending on the intracellular pH (Alili et al., 2010; Amin et al., 2011; Wason et al., 2013). Thus, nCeO 2 constitute a promising cancer treatment (Alili et al., 2010; Colon et al., 2010, 2009), and could also find applications for their neuroprotective (Das et al., 2007), wound healing (Chaudhury et al., 2012; Chigurupati et al., 2013) or angiogenesis promoting properties (Das et al., 2012). Antioxidant properties of nCeO 2 could result from oxygen vacancies in the crystal lattice surface caused by the presence of Ce in the trivalent state that could provide reaction sites for ROS trapping (Ciofani et al., 2014; Korsvik et al., 2007; Xue et al., 2011). "
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    • "The level of nanoceria surface functionalization with heparin determines the intracellular localization and ROS scavenging ability of these particles. Heparin–nanoceria was effective in reducing endothelial cell proliferation, indicating that they may have application in the control of angiogenesis in cancer in the future.40 It has been shown that CONPs have a unique property of inducing angiogenesis, which is critical for many physiological and pathophysiological processes and promotes the formation of new blood vessels from existing blood vessels.40 "
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    • "In recent years, researchers have begun to investigate the biological properties of the cerium oxide of CeO2. It has been proven that cerium oxide is able to induce angiogenesis through its direct effect on the modulation of oxygen in intracellular environments [115]. In turn, Lord et al. [116] have studied the impact of cerium oxide on human monocytes, based on its ability to scavenge ROSs. "
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