Fullerene C₆₀ as a multifunctional system for drug and gene delivery.
ABSTRACT The fullerene family, and especially C(60), has delighted the scientific community during the last 25 years with perspective applications in a wide variety of fields, including the biological and the biomedical domains. Several biomedical uses have been explored using water-soluble C(60)-derivatives. However, the employment of fullerenes for drug delivery is still at an early stage of development. The design and synthesis of multifunctionalized and multimodal C(60) systems able to cross the cell membranes and efficiently deliver active molecules is an attracting challenge that involves multidisciplinary strategies. Promising results have emerged in the last years, bringing fullerenes again to the front of interest. Herein, the state of the art of this emerging field is presented and illustrated with some of the most representative examples.
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ABSTRACT: The aim of the paper was to provide the physico-chemical characterization of key process leading to amplification of antitumor effect of antibiotic Doxorubicin (Dox) in vivo and in vitro and occurring at molecular level through complexation with C60 fullerene. A wide range of physico-chemical tools was used such as UV/Vis and NMR spectroscopies, atomic force microscopy, isothermal titration calorimetry and zeta-potential methods. The unusual thermodynamic behavior of the complexation process was reported, featuring unexpected and, to certain extent, contradictory experimental observations. The explanation of the obtained results was proposed resulting in creation of a general view on aromatic drug binding with C60 fullerene. Based on these results some important practical outcomes for anticancer therapy were formulated.Physical Chemistry Chemical Physics 09/2014; 16(42):23164. · 4.20 Impact Factor
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ABSTRACT: Derivatives of fullerene (C60) as photosensitizers have rarely been studied as delivery carrier materials. The focus of this study was to explore the potential advantages of diadduct malonic acid-fullerene (DMA-C60) as delivery carrier materials and combination of chemo–phototherapy of some tumors. In this study, DMA-C60 and docetaxel (DTX) were coentrapped in micelles (MCs) (DMA-C60/DTX-MC). The addition of DMA-C60 could obviously improve static stability and decrease critical MC concentration of DTX-MC without hemolysis. The sustained release of DTX and DMA-C60 could be achieved, following Higuichi and first-order model, respectively. DMA-C60 could still produce reactive oxygen species efficiently in HeLa cells after encapsulation in MC. The addition of DMA-C60 under irradiation caused DTX-MC more stronger cytotoxicity, cell cycle changes, and more early apoptotic cells in vitro. More importantly, after intravenous injection, the addition of DMA-C60 in DTX-MC could result in 2.25-fold and 4.57-fold longer mean residence time compared with DTX-MC and Duopafei®, increase drug intratumoral distribution and decrease drug distribution in heart and kidney, and enhance antitumor effect under irradiation without body weight loss. These results suggested tremendous promise of DMA-C60 as carrier materials of MC and significant advantages in combination of chemo–phototherapy of some tumors. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm SciJournal of Pharmaceutical Sciences 08/2014; · 3.13 Impact Factor
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ABSTRACT: The physical sorption of a series of cyclophosphamide drug derivatives with formula where x=2, X=F (2), Cl (3), Br (4); x=3, X=F (5), Cl (6), Br (7) and x=4, X=F (8), Cl (9), Br (10) on the surface of fullerene C60 was studied using density functional theory (DFT) at B3LYP and B3PW91 levels. The most negative binding energies obtained using the B3LYP approach and corrected for geometrical BSSE and dispersion energies (gCP-D3-ΔEbinding) were measured for compounds 8 (among isolated drugs) and 13 (among complexes). The dipole moments of isolated drugs were obtained close to those of their complexes with C60 (∼4.0-5.5 Debye) indicating their hydrophililic nature that is an appropriate property appealing for drug delivery in biological media. The adsorption of all drugs on the surface of fullerene was endergonic with all of the ΔGadsorption>0. The ΔHadsorption values at B3PW91 level were only negative for complexes 14-16 indicating their exothermic adsorption nature. The HOMO-LUMO band gaps of complexes 11-19 were about 2.7eV and are comparable with the gap in C60 but are much smaller than the gaps in isolated drugs 2-10 (6.5-8.0eV) reflecting the increase in electrical conductivities upon complexation. The QTAIM data supported the covalent character of the C-O, C-N and N-H bonds, the intermediate character of PO, P-O and P-N bonds while the electrostatic nature of PO…C(fullerene) interactions. According to the gCP-D3-ΔEbinding binding energies and ΔHadsorption values at B3LYP level, it seems that the complexes 12 and 13 can be the most promising prodrug+carrier delivery systems.Journal of Molecular Graphics and Modelling. 01/2014;