ABSTRACT
Title
Functionalized fullerenes as nanocarriers for anticancer drugs
Authors
M. Lucafò
Doctorate School in Nanotechnology
Dept. of Life Sciences - University of Trieste, Italy
Doctorate School in Nanotechnology
Dept. of Life Sciences - University of Trieste, Italy
Abstract
The use of nanomaterials to diagnose and treat diseases has been a goal for scientists ever since the advent of methods to manipulate molecules at the nanometer scale [1]. Fullerenes (C60) are among the nanomaterials being investigated for diagnostic and therapeutic modalities. In particular they might be suitable vectors for drug delivery due to their small size, large surface area and characteristic solubility [2]. Little is known about how fullerenes enter cells, what organelles they target, and the time course for their cellular deposition. The cytotoxicity of different fullerenes, the process of cell recognition and the mechanism of cellular uptake are the subject of this work.
Functionalized fullerenes were synthesized by 1,3-dipolar cycloaddition of azomethine ylides to the C60cage. This is a versatile reaction to modify C60in terms of water-solubility and to offer an anchor point for the attachment of other moieties. Cell cytotoxicity on human mammary carcinoma cell lines, evaluated with the MTT test and further confirmed by a flow cytometry approach with DiOC6 probe and PI analyses, showed two of the tested compounds free of any necrotic or apoptotic effect, even at the highest concentration (25µM) and after a long lasting cell exposure (72h). Cell uptake and internalization of the less cytotoxic, fluorescein-labeled compound, reaches the highest fluorescence peak within 12 h after treatment, with a tendency to decrease and persist in the following hours up to 72h; this process was evaluated by flow cytometry and confirmed by confocal microscopy. These results suggest a strong interaction between the tested fullerene and mammalian cells and a significant ability of this compound to get into tumour cells. So far, the functionalized fullerene can be considered a suitable vector to deliver anticancer agents to tumour cells.
[1] Dellinger A et al. Uptake and distribution of fullerenes in human mast cells. Nanomedicine: NBM 2010;6:575-581.
[2] Zhanga LW et al. Endocytic mechanisms and toxicity of a fullerene in human cells. Tox. Lett. 2009;191:149-157.
Functionalized fullerenes were synthesized by 1,3-dipolar cycloaddition of azomethine ylides to the C60cage. This is a versatile reaction to modify C60in terms of water-solubility and to offer an anchor point for the attachment of other moieties. Cell cytotoxicity on human mammary carcinoma cell lines, evaluated with the MTT test and further confirmed by a flow cytometry approach with DiOC6 probe and PI analyses, showed two of the tested compounds free of any necrotic or apoptotic effect, even at the highest concentration (25µM) and after a long lasting cell exposure (72h). Cell uptake and internalization of the less cytotoxic, fluorescein-labeled compound, reaches the highest fluorescence peak within 12 h after treatment, with a tendency to decrease and persist in the following hours up to 72h; this process was evaluated by flow cytometry and confirmed by confocal microscopy. These results suggest a strong interaction between the tested fullerene and mammalian cells and a significant ability of this compound to get into tumour cells. So far, the functionalized fullerene can be considered a suitable vector to deliver anticancer agents to tumour cells.
[1] Dellinger A et al. Uptake and distribution of fullerenes in human mast cells. Nanomedicine: NBM 2010;6:575-581.
[2] Zhanga LW et al. Endocytic mechanisms and toxicity of a fullerene in human cells. Tox. Lett. 2009;191:149-157.