Fullerene C-60 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 interest on functionalized fullerenes in the field of nanomedicine has seen a significant increase in the past decade. However, the different methods employed to increase C60 solubility profoundly influence the physicochemical properties and the toxicological effects of these compounds, thus complicating the evaluation of their toxicity and potential therapeutic use. Here we report a whole-transcriptome RNA-seq analysis assessing the effect of two fullerenes (1 and 2) on gene expression in the human MCF7 cell line. Although these two compounds had previously been characterized by in vitro studies as having a cytotoxic and null effect respectively, to date the mechanisms at the basis of this different behavior and, more in general, at the basis of the effect of most fullerene derivatives in living cells are still completely unknown. Our data evidence that: a) fullerene 2 caused a significant, time-dependent alteration of gene expression, whereas 1 only had a negligible effect; b) the biological processes mostly influenced over the 48hours experimental time course were transcription, protein synthesis, cell cycle progression and cell adhesion; c) the gene expression signature of 2-treated cells was strikingly similar to those induced by selective inhibitors of mTOR signaling, thus suggesting an effect on this pathway for fullerene 2. Our work represents the first approach towards the application of RNA-seq to the study of the molecular mechanisms underlying the interaction of fullerenes with cellular systems and provides an objective view of the feasibility and the safety of these nanomaterials for a medical application.Toxicology 10/2013; 314(1). DOI:10.1016/j.tox.2013.10.001 · 3.75 Impact Factor
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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.Biochimica et Biophysica Acta (BBA) - Biomembranes 09/2013; 1828(9):2007-2014. DOI:10.1016/j.bbamem.2013.05.009 · 3.43 Impact Factor
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ABSTRACT: Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C60 are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C60 exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C60 nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity was neither related to the transcriptional control (RT-qPCR analysis) nor to the direct action of nonphotoexcited C60 nano/microparticles on the protein (in vitro results) but probably involved a posttranscriptional or posttranslational modulation of this enzymatic activity. Taken together these findings provided further evidence of toxic effects on brain after C60 exposure.01/2013; 2013:623789. DOI:10.1155/2013/623789