Fullerenes (C 60) represent important carbon nanoparticles, widely investigated for diagnostic and therapeutic uses, mainly because they are characterized by a small size (between 7 and 10A °) and a large surface area. The cytotoxicity of two fullerene derivatives, functionalized by 1, 3-dipolar cycloaddition of azomethine ylides to the C 60 cage (1 and 2), the mechanism of cellular uptake (studied with a fluorescein-bearing derivative of 1, hereafter called derivative 3), and the intracellular distribution are the subject of this work.Cell cytotoxicity on human mammary carcinoma cell line (MCF7), evaluated with the MTT test and further confirmed by a flow cytometry approach with DiOC 6 and PI probes, showed that derivative 1 was free of necrotic or apoptotic effects even after a long lasting cell exposure. Cell uptake and internalization of derivative 3 reach their zenith within 12 h after treatment, with a tendency to persist up to 72 h; this process was evaluated by flow cytometry and confirmed by confocal microscopy. Thus, it appears that a compound such as derivative 1 may be unspecifically taken up by MCF7 cells, in which it distributes throughout the cytoplasm, apparently avoiding any co-localization within the nucleus and secretory granules. These results suggest a strong interaction between the tested fullerene and mammalian cells and a significant ability of this compound to enter tumor cells, therefore resulting to be a suitable vector to deliver anticancer agents to tumor cells. © 2012 Springer Science+Business Media B.V.

Study of a potential drug delivery system based on carbon nanoparticles: effects of fullerene derivatives in MCF7 mammary carcinoma cells

FABBRO, Chiara;
2012

Abstract

Fullerenes (C 60) represent important carbon nanoparticles, widely investigated for diagnostic and therapeutic uses, mainly because they are characterized by a small size (between 7 and 10A °) and a large surface area. The cytotoxicity of two fullerene derivatives, functionalized by 1, 3-dipolar cycloaddition of azomethine ylides to the C 60 cage (1 and 2), the mechanism of cellular uptake (studied with a fluorescein-bearing derivative of 1, hereafter called derivative 3), and the intracellular distribution are the subject of this work.Cell cytotoxicity on human mammary carcinoma cell line (MCF7), evaluated with the MTT test and further confirmed by a flow cytometry approach with DiOC 6 and PI probes, showed that derivative 1 was free of necrotic or apoptotic effects even after a long lasting cell exposure. Cell uptake and internalization of derivative 3 reach their zenith within 12 h after treatment, with a tendency to persist up to 72 h; this process was evaluated by flow cytometry and confirmed by confocal microscopy. Thus, it appears that a compound such as derivative 1 may be unspecifically taken up by MCF7 cells, in which it distributes throughout the cytoplasm, apparently avoiding any co-localization within the nucleus and secretory granules. These results suggest a strong interaction between the tested fullerene and mammalian cells and a significant ability of this compound to enter tumor cells, therefore resulting to be a suitable vector to deliver anticancer agents to tumor cells. © 2012 Springer Science+Business Media B.V.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10278/34795
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