Twenty Years of Promises: Fullerene in Medicinal Chemistry
Many biological activities have been envisioned for fullerenes and some of them seem to be very promising. The lack of solubility in biologically friendly environments is the major obstacle in the development of this field. The possibility of multiple fuctionalization can be exploited to get more soluble compounds but, up to now, only a few polyadducts, presenting perfectly defined geometry, can be selectively prepared avoiding long purification processes.
The toxicity of this third allotropic form of carbon is an aspect related to application in medicine and biology, while the concern about the environmental impact is due to the industrial production of fullerenes. Many studies are dedicated to both aspects and, so far, it is not possible to have a definitive answer although the current findings allow some optimistic vision.
In this chapter the main biological applications of fullerene and fullerene derivatives will be reviewed, with special attention to the most recent advances in this field. Antiviral and antibacterial activity, enzymatic inhibition, and DNA photocleavage are some aspects considered herein, together with the use of these nanostructures as possible vectors for drug and gene delivery. The most promising applications include the use of endohedral fullerenes, filled by gadolinium, in magnetic resonance imaging (MRI) and the antioxidant capacity exploitation of some tris-adducts and fullerols.
KeywordsAntibacterial activity anticancer activity antioxidant properties antiviral activity cell protection contrast agent drug delivery photodynamic therapy protein interaction radiotherapy toxicity
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- Baker G, Gupta A, Clark M, Valenzuela B, Staska L, Harbo S, Pierce J, Dill J (2007) Inhalation toxicity and lung toxicokinetics of C60 fullerene nanoparticles and microparticles. Toxicol. Sci.: doi:10.1093/toxsci/kfm1243Google Scholar
- Belgorodsky B, Fadeev L, Kolsenik J, Gozin M (2006) Formation of a soluble stable complex between pristine C60-fullerene and a native blood protein. Chem. Biol. Chem. 7:1783-1789.Google Scholar
- Bianco A, Da Ros T (2007) Biological applications of fullerenes. In: Langa F, Nierengarten J-F (eds.) Fullerenes - Principles and Applications. Royal Chemical Society, Cambridge, pp. 301-328.Google Scholar
- Dugan LL, Lovett E, Cuddihy S, Ma B-W, Lin T-S, Choi DW (2000) Carboxyfullerenes as neuro-protective antioxidants. In: Kadish KM, Ruoff RS (eds.) Fullerenes: Chemistry, Physics, and Technology. Wiley, New York, pp. 467-479.Google Scholar
- Iwamoto Y, Yamakoshi Y (2006) A highly water-soluble C60-NVP copolymer: A potential material for photodynamic therapy. Chem. Commun. 4805-4807.Google Scholar
- Klumpp C, Lacerda L, Chaloin O, Da Ros T, Kostarelos K, Prato M, Bianco A (2007) Multifunctionalised cationic fullerene adducts for gene transfer: Design, synthesis and DNA complexation. Chem. Commun. 3762-3764.Google Scholar
- Martín N (2006) New challenges in fullerene chemistry. Chem. Commun. 2093-2104.Google Scholar
- Mashino T, Shimotohno K, Ikegami N, Nishikawa D, Okuda K, Takahashi K, Nakamura S, Mochizuki M (2005) Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg. Med. Chem. Lett. 15:107-1109.CrossRefGoogle Scholar
- Porter AE, Gass M, Muller K, Skepper JN, Midgley P, Welland M (2007) Visualizing the uptake of C60 to the cytoplasm and nucleus of human monocyte-derived macrophage cells using energy-filtered transmission electron microscopy and electron tomography. Environ. Sci. Technol. 41:3012-3017.CrossRefGoogle Scholar
- Quick K, Dugan L (2004) Fullerene derivative (C3) functions as a SOD mimetic by reducing age-related increase in superoxide levels and prevention of age-related loss of mitochondrial membrane potential in brain. Free Rad. Biol. Med. 37:S163-S163.Google Scholar
- Ryan JJ, Bateman HR, Stover A, Gomez G, Norton SK, Zhao W, Schwartz LB, Lenk R, Kepley CL (2007) Fullerene nanomaterials inhibit the allergic response. J. Immunol. 179:665-672.Google Scholar
- Sarova GH, Da Ros T, Guldi DM (2006) Fullerene-based devices for biological applications. In: Kumar C (ed.) Nanodevices for the Life Science, Vol. 4. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp. 352-389.Google Scholar
- Schinazi RF, Sijbesma RP, Srdanov G, Hill CL, Wudl F (1993) Synthesis and virucidal activity of a water soluble, configurationally stable, derivatized C60 fullerene. Antimicrob. Agents Chemother. 37:1707-1710.Google Scholar
- Schuster DI, Wilson LJ, Kirschner AN, Schinazi RF, Schlueter-Wirtz S, Tharnish P, Barnett T, Ermolieff J, Tang J, Brettreich M, Hirsch A (2000) In: Martin N, Maggini M, Guldi DM (eds.) Fullerene 2000 - Functionalized Fullerenes, Vol. 9. The Electrochemical Society, Pennington, NJ, pp. 267-270.Google Scholar
- Tagmatarchis N, Shinohara H (2001) Fullerene in medicinal chemistry and their biological applications. Mini Rev. Med. Chem. 1:339-348.Google Scholar
- Ying Q, Zhang J, Liang D, Nakanishi W, Isobe H, Nakamura E, Chu B (2005) Fractal behavior of functionalized fullerene aggregates. I. Aggregation of two-handed tetraaminofullerene with DNA. Langmuir 21:9824-9831.Google Scholar