Article

Uptake and distribution of fullerenes in human mast cells

Luna Innovations Inc., Nanoworks Division, Danville, Virginia 24541, USA.
Nanomedicine: nanotechnology, biology, and medicine (Impact Factor: 6.16). 02/2010; 6(4):575-82. DOI: 10.1016/j.nano.2010.01.008
Source: PubMed

ABSTRACT

Fullerenes are carbon cages of variable size that can be derivatized with various side chain moieties resulting in compounds that are being developed into nanomedicines. Although fullerene use in several preclinical in vitro and in vivo models of disease has demonstrated their potential as diagnostic and therapeutic agents, little is known about how they enter cells, what organelles they target, and the time course for their cellular deposition. Fullerenes (C(70)) that have already been shown to be potent inhibitors of mast cell (MC)-mediated allergic inflammation were conjugated with Texas red (TR) and used in conjunction with confocal microscopy to determine mechanisms of uptake, the organelle localization, and the duration they can be detected in situ. We show that C(70)-TR are nonspecifically endocytosed into MCs, where they are shuttled throughout the cytoplasm, lysosomes, mitochondria, and into endoplasmic reticulum at different times. No nuclear or secretory granule localization was observed. The C(70)-TR remained detectable within cells at 1 week. These studies show that MCs endocytose fullerenes, where they are shuttled to organelles involved with calcium and reactive oxygen species production, which may explain their efficacy as cellular inhibitors. From the clinical editor: Fullerenes are carbon cages of variable size that have already been shown to be potent inhibitors of mast cell (MC)-mediated allergic inflammation. These were conjugated with Texas red (TR) and used in conjunction with confocal microscopy to determine mechanisms of uptake, the organelle localization, and duration, demonstrating that MCs endocytose fullerenes, which are shuttled to organelles involved with calcium and reactive oxygen species production. This intracellular trafficking may explain the efficacy of fullerenes as cellular inhibitors.

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    • "Among these nanoscale chemical structures, fullerenes represent an important source of the socalled biocompatible molecules because of their capacity to be in contact with cells and biological tissues without altering their behaviour [3]. Some of these substances were shown to be capable to cross cells without affecting their viability [4] [5]; others were demonstrated to be suitable as substrates for the growth of cells and tissues of importance for regenerative medicine and cell therapies [6]. They are also supposed to be good drug carriers in that they might use the enhanced permeability retention for selective accumulation of cytotoxic agents into solid tumour masses [7] [8]. "
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    ABSTRACT: Two fullerene derivatives (fullerenes 1 and 2), bearing a hydrophilic chain on the pyrrolidinic nitrogen, were developed with the aim to deliver anticancer agents to solid tumors. These two compounds showed a significantly different behaviour on human neoplastic cell lines in vitro in respect to healthy leukocytes. In particular, the pyrrolidinium ring on the fullerene carbon cage brings to a more active compound. In the present work, we describe the effects of these fullerenes on primary cultures of human monocytes and macrophages, two kinds of immune cells representing the first line of defence in the immune response to foreign materials. These compounds are not recognized by circulating monocytes while they get into macrophages. The evaluation of the pronecrotic or proapoptotic effects, analysed by means of analysis of the purinergic receptor P2X7 activation and of ROS scavenging activity, has allowed us to show that fullerene 2, but not its analogue fullerene 1, displays toxicity, even though at concentrations higher than those shown to be active on neoplastic cells.
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    • "Among these nanoscale chemical structures, fullerenes represent an important source of the socalled biocompatible molecules because of their capacity to be in contact with cells and biological tissues without altering their behaviour [3]. Some of these substances were shown to be capable to cross cells without affecting their viability [4] [5]; others were demonstrated to be suitable as substrates for the growth of cells and tissues of importance for regenerative medicine and cell therapies [6]. They are also supposed to be good drug carriers in that they might use the enhanced permeability retention for selective accumulation of cytotoxic agents into solid tumour masses [7] [8]. "

    Full-text · Article · Jan 2014 · BioMed Research International
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    • "It can adsorb, however, to the protein domains of the membrane by van der Waals or dipolar interactions [31]. These assumptions are in agreement with data obtained via molecular modeling [25] [32] as well as experimental data [26] [33] [34]. The leakage of potassium ions from the cells is related to disruption of active membrane transport and a result of the decrease in ATP levels, which can occur during prolonged incubation of erythrocytes [35]. "
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    ABSTRACT: The present study was aimed at investigating the effect of fullerenol C60(OH)36 on chosen parameters of the human erythrocyte membrane and the preliminary estimation of the properties of fullerenol as a potential linking agent transferring the compounds (e.g., anticancer drugs) into the membrane of erythrocytes. The results obtained in this study confirm the impact of fullerenol on erythrocyte cytoskeletal transmembrane proteins, particularly on the band 3 protein. The presence of fullerenol in each of the concentrations used prevented degradation of the band 3 protein. The results show that changes in the morphology of red blood cells caused by high concentrations of fullerenol (up to 150 mg/L) did not lead to increased red blood cell hemolysis or the leakage of potassium. Moreover, fullerenol slightly prevented hemolysis and potassium efflux. The protective effect of fullerenol at the concentration of 150 mg/L was 20.3%, and similar results were obtained for the efflux of potassium. The study shows that fullerenol slightly changed the morphology of the cells and, therefore, altered the intracellular organization of erythrocytes through the association with cytoskeletal proteins.
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