Fullerene C(60) as a multifunctional system for drug and gene delivery. Nanoscale 3:4035-4041

Center of Excellence for Nanostructured Materials (CENMAT), Department of Chemical and Pharmaceutical Sciences, and INSTM, Unit of Trieste University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy.
Nanoscale (Impact Factor: 7.39). 09/2011; 3(10):4035-41. DOI: 10.1039/c1nr10783f
Source: PubMed


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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    • "To solve the dilemma on the optimal sizes for lung-targeted delivery, stable submicrometer-sized complex prepared prior to intravenous injection must grow into micrometer-sized particles under physiological conditions, release drugs at lung capillaries, and escape from the lung when the drug delivery is complete. In light of the diverse aggregation behavior of fullerenes in water14, their ability to protect DNA from degradation, and in vitro and in vivo gene delivery151617, we hypothesized that a cationic fullerene could serve as a carrier for the delivery of small interfering RNA (siRNA) for RNA interference (RNAi) therapeutics in vivo1819. We report here on the lung-specific delivery of siRNA using a cationic fullerene, tetra(piperazino)fullerene epoxide (TPFE) (Fig. 1)20. "
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    ABSTRACT: The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications.
    Scientific Reports 05/2014; 4:4916. DOI:10.1038/srep04916 · 5.58 Impact Factor
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    • "By testing the effects of two ROS scavengers, a singlet oxygen scavenger, sodium azide, and a hydroxyl radical scavenger mannitol, the inhibitory effects were significantly reduced, indicating a possible ROS-related mechanism.25 The fullerene–oligonucleotide conjugates, along with the multifunctionalized cationic fullerene adducts that were able to bind DNA,67,68 add further support for the use of fullerenes in gene therapy. "
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    ABSTRACT: Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene-biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene-biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene-biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.
    International Journal of Nanomedicine 01/2014; 9(1):77-92. DOI:10.2147/IJN.S52829 · 4.38 Impact Factor
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    • "Nowadays carbon nanotechnologies can be considered as a truly interdisciplinary subject, bridging material science with medicine. Fullerenes (C 60 ) play an important role in this field and are currently explored for biomedical applications, due to their potential use as Magnetic Resonance Imaging contrast agents (Cagle et al., 1999) and gene or drug delivery carriers (Lucafò et al., 2012; Montellano et al., 2011). Nevertheless, at the current stage, these studies are limited to in vitro and in vivo preclinical data, not having reached the phase of clinical trials yet. "
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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 · 3.62 Impact Factor
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