Fullerene medicine is a new but rapidly growing research subject. Fullerene has a number of desired structural, physical and chemical properties to be adapted for biological use including antioxidants, anti-aging, anti-inflammation, photodynamic therapy, drug delivery, and magnetic resonance imaging contrast agents. Chemical functionalization of fullerenes has led to several interesting compounds with very promising preclinical efficacy, pharmacokinetic and safety data. However, there is no clinical evaluation or human use except in fullerene-based cosmetic products for human skincare. This article summarizes recent advances in liposome formulation of fullerenes for the use in therapeutics and molecular imaging.
Ross, T.; Prato, M. Medicinal chemistry with fullerenes and fullerene derivatives. Chem. Commun. 1999, 8, 663–669.
[4]
Nakamura, E.; Isobe, H. Functionalized fullerenes in water. The first 10 years of their chemistry, biology, and nanoscience. Acc. Chem. Res. 2003, 36, 807–815.
[5]
Bosi, S.; da Ros, T.; Spalluto, G.; Prato, M. Fullerene derivatives: An attractive tool for biological applications. Eur. J. Med. Chem. 2003, 38, 913–923.
Dugan, L.L.; Turetsky, D.M.; Du, C.; Lobner, D.; Wheeler, M.; Almli, C.R.; Shen, C.K.F.; Luh, T.Y.; Choi, D.W.; Lin, T.S. Carboxyfullerenes as neuroprotective agents. Proc. Natl. Acad. Sci. USA 1997, 94, 9434–9439.
[15]
Brettreich, M.; Hirsch, A. A highly water-soluble dendro[60]fullerene. Tetrahedron Lett. 1998, 39, 2731–2734.
[16]
Johnston, H.J.; Hutchison, G.R.; Christensen, F.M.; Aschberger, K.; Stone, V. The biological mechanisms and physicochemical characteristics responsible for driving fullerene toxicity. Toxicol. Sci. 2010, 114, 162–182.
[17]
Bensasson, R.V.; Bienvenue, E.; Dellinger, M.; Leach, S.; Seta, P.J. C60 in model biological systems. A visible-UV absorption study of solvent-dependent parameters and solute aggregation. J. Phys. Chem. 1994, 98, 3492–3496.
[18]
Hungerbuhler, H.; Guldi, D.M.; Asmus, K.D. Incorporation of C60 into artificial lipid membranes. J. Am. Chem. Soc. 1993, 115, 3386–3390.
[19]
Zhou, Z.; Schuster, D.I.; Wilson, S.R. Tether directed selective synthesis of fulleropyrrolidine bisadducts. J. Org. Chem. 2006, 71, 1545–1551.
Zhou, Z.; Magriotis, P.A. A new method for the functionalization of [60]fullerene: An unusual 1,3-dipolar cycloaddition pathway leading to a C60 housane derivative. Org. Lett. 2005, 7, 5849–5851.
Rossi, G. Partitioning and solubility of C60 fullerene in lipid membranes. Phys. Scr. 2013, 87, 058503.
[25]
Zupanc, J.; Drobne, D.; Drasler, B.; Valant, J.; Iglic, A.; Kralj-Iglic, V.; Makovec, D.; Rappolt, M.; Sartori, B.; Kogej, K. Experimental evidence for the interaction of C-60 fullerene with lipid vesicle membranes. Carbon 2012, 50, 1170–1178.
[26]
Bouropoulos, N.; Katsamenis, O.L.; Cox, P.A.; Norman, S.; Kallinteri, P.; Favretto, M.E.; Yannopoulos, S.N.; Bakandritsos, A.; Fatouros, D.G. Probing the perturbation of lecithin bilayers by unmodified C60 fullerenes using experimental methods and computational simulations. J. Phys. Chem. 2012, 116, 3867–3874.
[27]
Zhan, W.; Jiang, K. A modular photocurrent generation system based on phospholipid-assembled fullerenes. Langmuir 2008, 24, 13258–13261.
[28]
Gan, L.; Huang, S.; Zhang, X.; Zhang, A.; Cheng, B.; Cheng, H.; Li, X.; Shang, G. Fullerenes as a tert-butylperoxy radical trap, metal catalyzed reaction of tert-butyl hydroperoxide with fullerenes, and formation of the first fullerene mixed peroxides. J. Am. Chem. Soc. 2002, 124, 13384–13385.
[29]
Birkett, P.R.; Avent, A.G.; Darwish, A.D.; Kroto, H.W.; Taylor, R.; Walton, D.R.M. Formation and characterization of C70Cl10. J. Chem. Soc. Chem. Commun. 1995, 683–684.
[30]
Scuseria, G.E. The equilibrium structure of C70. An ab initio Hartree-Fock study. Chem. Phys. Lett. 1991, 180, 451–469.
[31]
Lens, M.; Medenica, L.; Citernesi, U. Antioxidative capacity of C60 (buckminsterfullerene) and newly synthesized fulleropyrrolidine derivatives encapsulated in liposomes. Biotechnol. Appl. Biochem. 2008, 51, 135–140.
[32]
Williams, R.M.; Crielaard, W.; Hellingwerf, K.J.; Verhoeven, J.W. Incorporaiton of fullerene-C60 and C60 adducts in micellar and vesicular supermolecular assemblies: Introductory flash photolysis and photoredox experiments in micelles. Recl. Trav. Chim. Pays-Bas 1996, 115, 72–76.
Norton, S.; Wijesinghe, D.; Dellinger, A.; Sturgill, J.; Zhou, Z.; Barbour, S.; Chalfant, C.; Conrad, D.; Kepley, C.L. Epoxyeicosatrienoic acids are involved in the C70 fullerene derivative-induced control of allergic asthma. J. Allergy Clin. Immunol. 2012, 130, 761–769.
[35]
Dellinger, A.; Zhou, Z.; Connor, J.; Madhankumar, A.B.; Pamujula, S.; Sayes, C.M.; Kepley, C.L. Application of fullerenes in nanomedicine: An update. Nanomedicine 2013, 8, 1191–1208.
[36]
Yamakoshi, Y. Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2？？ versus 1O2. J. Am. Chem. Soc. 2003, 125, 12803–12809.
[37]
Ikeda, A.; Doi, Y.; Hashizume, M.; Kikuchi, J.; Konishi, T. An extremely effective DNA photocleavage utilizing functionalized liposomes with a fullerene-enriched lipid bilayer. J. Am. Chem. Soc. 2007, 129, 4140–4141.
[38]
Ikeda, A. Efficient photoclevage of DNA utilising water-soluble lipid membrane-incorporated [60]fullerenes prepared using a [60]fullerene exchange method. Org. Biomol. Chem. 2005, 3, 2907–2909.
[39]
Ikeda, A.; Kawai, Y.; Kikuchi, J.; Akiyama, M.; Nakata, E.; Uto, Y.; Hori, H. Formation and regulation of fullerene-incorporation in liposomes under the phase transition temperature. Org. Biomol. Chem. 2011, 9, 2622–2627.
[40]
Du, C.; Xiong, H.; Ji, H.; Liu, Q.; Xiao, H.; Yang, Z. The antiviral effect of fullerene-liposome complex against influenza virus (H1N1) in vivo. Sci. Res. Essays 2012, 7, 705–711.
[41]
Dellinger, A.; Olson, J.; Link, K.; Vance, S.; Sandros, M.G.; Yang, J.; Zhou, Z. Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 2013, 15, 7.
[42]
McFarland, D.K.; Walker, K.L.; Lenk, R.P.; Wilson, S.R.; Kumar, K.; Kepley, C.L.; Garbow, J.R. Hydrochalarones: A novel endohedral metallofullerene platform for enhancing magnetic resonance imaging contrast. J. Med. Chem. 2008, 51, 3681–3683.
[43]
Podrez, E.A.; Poliakov, E.; Shen, Z. Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36. J. Biol. Chem. 2002, 277, 38503–38518.
[44]
Amirbekian, V.; Lipinski, M.J.; Briley-Saebo, K.C. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc. Natl. Acad. Sci. USA 2007, 104, 961–966.
[45]
Nunn, A.D.; Linder, K.E.; Tweedle, M.F. Can receptors be imaged with MRI agents? Q. J. Nucl. Med. 1997, 41, 155–162.
[46]
Zakharian, T.Y.; Seryshev, A.; Sitharaman, B.; Gilbert, B.E.; Knight, V.; Wilson, L.J. A fullerene-paclitaxel chemotherapeutic: Synthesis, characterization, and study of biological activity in tissue culture. J. Am. Chem. Soc. 2005, 127, 12508–12516.
[47]
Shinya, K.; Hisae, A.; Yasukazu, S.; Nobuhiko, M. Fullerene-C60 incorporated in liposome exerts persistent hydroxyl radical-scavenging activity and cytoprotection in UVA/B-irradiated keratinocytes. J. Nanosci. Nanotechnol. 2011, 11, 3814–3823.
[48]
Kato, S.; Kikuchi, R.; Aoshima, H.; Saitoh, Y.; Miwa, N. Defensive effects of fullerene-C60/liposome complex against UVA-induced intracellular reactive oxygen species generation and cell death in human skin keratinocytes HaCaT, associated with intracellular uptake and extracellular excretion of fullerene-C60. J. Photochem. Photobiol. B 2010, 98, 144–151.
[49]
Kato, S.; Aoshima, H.; Saitoh, Y.; Miwa, N. Fullerene-C60/liposome complex: Defensive effects against UVA-induced damages in skin structure, nucleus and collagen type I/IV fibrils, and the permeability into human skin tissue. J. Photochem. Photobiol. B 2010, 98, 99–105.
[50]
Brettreich, M.; Burghardt, S.; Bottcher, C.; Bayerl, T.; Bayerl, S.; Hirsch, A. Globular amphiphiles: Membraneforming hexaadducts of C60. Angew. Chem. Int. Ed. 2000, 39, 1845–1848.
[51]
Maierhofer, A.P.; Brettreich, M.; Burghardt, S.; Vostrowsky, O.; Hirsch, A.; Langridge, S.; Bayerl, T.M. Structure and electrostatic interaction properties of monolayers of amphiphilic molecules derived from C60-fullerenes: A film balance, neutron, and infrared reflection study. Langmuir 2000, 16, 8884–8891.
[52]
Partha, R.; Lackey, M.; Hirsch, A.; Casscells, S.W.; Conyers, J.L. Self-assembly of amphiphilic C60 fullerene derivatives into nanoscale supramolecular structures. J. Nanobiotechnol. 2007, 5, 6.
Danila, D.; Golunski, E.; Partha, R.; McManus, M.; Little, T.; Conyers, J. Buckysomes: New nanocarriers for anticancer drugs. J. Pharm. 2013, 2013, doi:10.1155/2013/390425.
