Endocytic mechanisms and toxicity of a functionalized fullerene in human cells

Center for Chemical Toxicology Research and Pharmacokinetics, Department of Clinical Science, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Toxicology Letters (Impact Factor: 3.26). 09/2009; 191(2-3):149-57. DOI: 10.1016/j.toxlet.2009.08.017
Source: PubMed

ABSTRACT Derivatized fullerenes could be used in biomedical applications and be suitable vectors for drug delivery due to their small size, large surface area and solubility. However, the interactions of derivatized fullerenes with biological systems and cells are not well understood. A water-soluble fullerene-substituted phenylalanine (Bucky amino acid, Baa) poly-lysine derivative with a FITC label (Baa-Lys(FITC)-(Lys)(8)-OH) was characterized by dynamic light scattering, transmission electron microscopy with negative staining, gel electrophoresis, zeta-potential, and UV/vis spectroscopy. Viability assays depicted the cytotoxicity was time, concentration and assay dependent. A decrease in ATP and glutathione at the high concentrations suggests that reactive oxygen species may be involved. Baa-Lys(FITC)-(Lys)(8)-OH was present near the cell membrane at 15 min and entered into the cytoplasm by 30 min but did not localize in the lysosomes. Endocytic inhibitors were used to investigate the uptake mechanism. These results showed that the endocytic pathways could be mediated by caveolae/lipid rafts and cytoskeletal components. A scavenger receptor inhibitor completely blocked the uptake of Baa-Lys(FITC)-(Lys)(8)-OH, suggesting a specific endocytic pathway was strongly involved in Baa-Lys(FITC)-(Lys)(8)-OH cellular uptake.

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Available from: Nancy A Monteiro-Riviere, Sep 26, 2015
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    • "Th e role of functionalized fullerene in a new emerging research area, nanobiotechnology, that includes nanomedicine and biomedical applications was reviewed with details (Satoh and Takayanagi 2006, Partha and Conyers 2009). It should be noted that toxicity of functionalized fullerene is not well understood (Zhang et al. 2009). Self-assembled spherical nanostructures derived from amphiphilic fullerene were used as nanocarrier called as buckysomes for paclitaxel, a highly hydrophobic anticancer drug. "
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    ABSTRACT: Hybrid magnetic nanoparticles composed from C60 fullerene and γ-Fe2O3 were synthesized by hydrothermal method. XRD, FT-IR, VSM, SEM, and HR-TEM were employed for characterizations. The magnetic saturation value of C60-γ-Fe2O3 magnetic nanoparticles was 66.5 emu g(- 1). Concentration of Fe in nanoparticles asdetermined by ICP-OES was 40.7% Fe. Particle size of C60-γ-Fe2O3 magnetic nanoparticles was smaller than 10 nm. Maximum adsorption capacity of C60-γ-Fe2O3 for flurbiprofen, a non-steroidal anti-inflammatory drug, was calculated from Langmuir isotherm as 142.9 mg g(- 1).
    Artificial Cells 08/2014; DOI:10.3109/21691401.2014.948182 · 1.02 Impact Factor
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    • "Various in vitro and in vivo safety assessments of fullerene C 60 and its derivatives have been reported previously (Metanawin et al. 2011; Nielsen et al. 2008; Zhang et al. 2009). Most studies have shown that fullerene C 60 and its derivatives are not genotoxic under in vitro conditions (Aoshima et al. 2010; Ema Pharmazie 68 (2013) 55 ORIGINAL ARTICLES Fig. 3: Effect of oral administration of PVP-fullerene C 60 on the histology of the colon in mice. "
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    ABSTRACT: The fullerene C60 is used in consumer products such as cosmetics owing to its antioxidative effects and is being developed for nanomedical applications. However, knowledge regarding the safety of fullerene C60, especially after oral administration, is sparse. Here, we examined the safety of fullerene C60 in mice after 7 d of exposure to orally administered polyvinylpyrrolidone (PVP)-wrapped fullerene C60 (PVP-fullerene C60). Mice treated with PVP-fullerene C60 showed few changes in the plasma levels of various markers of kidney and liver injury and experienced no significant hematologic effects. Furthermore, the histology of the colon of PVP-fullerene C60-treated mice was indistinguishable from that of control mice. These results suggest that PVP-fullerene C60 lacks toxicity after high-dose oral administration and indicate that PVP-fullerene C60 can be considered safe for oral medication. These data provide basic information that likely will facilitate the production of safe and effective forms of fullerene C60.
    Pharmazie 02/2013; 68(1):54-7. DOI:10.1691/ph.2013.2708 · 1.05 Impact Factor
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    • "The ability of fullerenes to be catalytically active therefore opens a new field of toxicology, where the toxic agents conduct interfering biochemical activities, rather than being passive particles that block mechanisms of the body. Given their potential interaction with several cellular factors, the unknown incubation time, and DNA-damaging properties (Yamakoshi et al. 2003; Markovic et al. 2007; Dhawan et al. 2006; Subach et al. 2009; Tokuyama et al. 1993; Zhang et al. 2009), their catalytic properties (Liang et al. 2009) and their membrane permeating properties (Nakagawa et al. 2011; Sadauskas et al. 2007; Jovanovicét al. 2011) leading to cell death through the formation of Neutrophil extracellular traps (NETs), fullerenes need to be classified as nanotoxicological particles which need to be studied in all their available forms before they can be applied in cosmetics, medicinal and other industrial scopes. Particularly, given that recent results (Henry et al. 2011) argue that fullerenes do not induce significant damage in fish, the mechanism of toxicological damage as stated in other studies must be elucidated, particularly according to structure–function activity studies. "
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    ABSTRACT: Nanotechnology globally represents a new direction within scientific development, where the atomic and electronic properties of molecules are used in a unique fashion to produce and construct new and exotic materials and products. Fullerenes (Bucky balls, C 60) constitute a particular group within the field of nanotechnology. Ful-lerenes find applications in medicine, industrial chemistry and electronics. However, there are several unanswered questions about fullerenes and their toxicological proper-ties. Most toxicological studies on fullerenes evolve around the in vitro and in vivo aspects of pristine C 60 along with chemically modified C 60 molecules. We reviewed toxi-cology reports on C 60 . We bring a critical and challenging evaluation of the electronic and quantum properties of C 60 molecules in context with the implications on cellular factors and metabolites. The evaluation shows that the reactivity and quantum chemical properties of C 60 can have unexpected effects in the cell, by principally absorbing metabolites, such as OH -and H ? ions and alter its reac-tivity. We thus challenge the present view of C 60 solely based on empirical studies, based on the electronic prop-erties of C 60 that vary considerably with their size and reaction path. A further example of this is the absorption of divalent zinc ions, which shows an increase in reactivity of the C 60 that presents an important pattern of chemical state, reactivity and toxicological potential. The results evaluate the toxicological potential of C 60 from a different angle than conventional, by applying a blend of critical review of the findings on C 60 toxicity, their chemical and electronic properties.
    Environmental Chemistry Letters 06/2012; DOI:10.1007/s10311-012-0387-x · 2.57 Impact Factor
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