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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Available from: Sanjay Singh, Sep 18, 2014
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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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    ABSTRACT: Cerium nanoparticles (nCeO2) are widely used in everyday products, as fuel and paint additives. Meanwhile, very few studies on nCeO2 sublethal effects on aquatic organisms are available. We tried to fill this knowledge gap by investigating short-term effects of nCeO2 at environmentally realistic concentrations on two freshwater invertebrates; the amphipod Gammarus roeseli and the bivalve Dreissena polymorpha, using an integrated multibiomarker approach to detect early adverse effects of nCeO2 on organism biology. Differences in the behaviour of the organisms and of nanoparticles in the water column led to differential nCeO2 bioaccumulations, G. roeseli accumulating more cerium than D. polymorpha. Exposure to nCeO2 led to decreases in the size of the lysosomal system, catalase activity and lipoperoxidation in mussel digestive glands that could result from nCeO2 antioxidant properties, but also negatively impacted haemolymph ion concentrations. At the same time, no strong adverse effects of nCeO2 could be observed on G. roeseli. Further experiments will be necessary to confirm the absence of severe nCeO2 adverse effects in long-term environmentally realistic conditions.
    Aquatic Toxicology 11/2014; 158. DOI:10.1016/j.aquatox.2014.11.004 · 3.45 Impact Factor
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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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    ABSTRACT: With the development of many nanomedicines designed for tumor therapy, the diverse abilities of cerium oxide nanoparticles (CONPs) have encouraged researchers to pursue CONPs as a therapeutic agent to treat cancer. Research data have shown CONPs to be toxic to cancer cells, to inhibit invasion, and to sensitize cancer cells to radiation therapy and chemotherapy. CONPs also display minimal toxicity to normal tissues and provide protection from various forms of reactive oxygen species generation. Differential cytotoxicity is important for anticancer drugs to distinguish effectively between tumor cells and normal cells. The antioxidant capabilities of CONPs, which enable cancer therapy protection, have also resulted in the exploration of these particles as a potential anticancer treatment. Taken together, CONPs might be a potential nanomedicine for cancer therapy and this review highlights the current research into CONPs as a novel therapeutic for the treatment of cancer.
    OncoTargets and Therapy 05/2014; 7:835-840. DOI:10.2147/OTT.S62057 · 2.31 Impact Factor
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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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    ABSTRACT: Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency.
    BioMed Research International 05/2014; 2014(2):178123. DOI:10.1155/2014/178123 · 3.17 Impact Factor
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