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Research in Medical & Engineering Sciences

Fullerene Trend in Biomedicine: Expectations and Reality

Tatjana A Skipa and Vitaly K Koltover*

Institute of Problems of Chemical Physics, Russia

*Corresponding author: Vitaly K Koltover, Institute of Problems of Chemical Physics, RAS, Chernogolovka, Moscow Region, Russia

Submission: November 11, 2019 Published: December 06, 2019

DOI: 10.31031/RMES.2019.08.000688

ISSN: 2576-8816
Volume8 Issue3

Opinion

Fullerenes are the third allotropic form of carbon, along with diamond and graphite, where carbon atoms are situated in vertices of the closed shells (cages) [1]. Since their discovery in 1985, fullerenes have attracted an attention of scientists not only because of their unique and beautiful structure but also as the materials for possible applications in engineering and medicine. Lots of fullerenes with hollow carbon cages were synthesized and chemically functionalized. Biomedical effects of such “empty” fullerenes are mostly defined by the chemical groups attached to the fullerene cage [1,2]. Besides, there are the so-called endohedral metallofullerenes (EMF) molecules of which contain one or more atoms, among them lanthanides or heavy elements like Pb or Bi trapped inside the carbon cage [3,4]. The goal of this editorial is to summarize the ideas of using fullerenes for biomedicine and express our opinion concerning the prospects of their application for therapeutic purposes.

The discovery of fullerenes has inspired the searching of novel fullerene-based drugs. Over the last three and a half decades, lots of so-called chemically functionalized fullerenes, with carbon cages containing up to 132 carbon atoms, were synthesized and tested in biomedical experiments. Some of these compounds have indeed displayed the beneficial medical effects, among them antioxidant properties and neuroprotective effects, healing tendencies against hepatitis C, antibacterial and anti-viral properties, even anti-HIV. There are the evidences regarding prospects of the fullerene derivatives in oncology and anti-aging medicine [2,5-15]. Some fullerenes, under the action of UV light, produce singlet oxygen and other reactive oxygen species and, thus, they can be used, for example, in the photodynamic therapy of cancer. Moreover, the beneficial effects of the fullerene derivatives against diabetes (type 2 diabetes mellitus) and Alzheimer disease were revealed in the experiments with rats [14,15]. Usual laboratory Wistar rats do not suffer from Diabetes Type II or Alzheimer disease, but the fullerene enthusiasm has apparently brought the Russian scientists out of the routine knowledge.

Endohedral metallofullerenes also appear to have a considerable promise in biomedicine. It has been suggested that EMF with the appropriate particle-emitting radionuclides inside, among them β-emitting 89Sr, 90Y, 47Sc, 64Cu, 149Pr, 153Sm, 166Ho, and 177Lu show promise for radiation medicine while the advances in the molecular biotechnology provide targeting vectors to deliver therapeutic doses of the ionizing radiation with high specificity to the metastatic cancer cells thereby decreasing irradiation of healthy tissues [16]. Recently, the radioactive Pb-EMF and Bi-EMF, with β-emitting 212Pb and a-emitting 212Bi inside the cage, and there malonic ester derivatives were prepared for the first time [17]. The anti-cancer effects of 212Pb, despite the favorable decay characteristics of this radionuclide, are usually limited because of the myelotoxicity resulting from accumulation of 212Pb in the bone marrow. In the experiments with mice it was found that 212Pb did not accumulate in the bone marrow after being administered within the endohedral fullerene, in contrast to the results with conventional poly amino carboxylate chelators for 212Pb. The EMF molecules encapsulate radionuclides more stably and, thus, could potentially play a valuable role in radioimmunotherapy [17].

It is well known that Gd(III)-based chelates are in current clinical use as contrast agents for magnetic-resonance imaging (MRI). Meanwhile, the "spin leakage" of the fullerene shell of EMF may provide the more effective relaxation mechanism through the contact coupling of the delocalized electron spin with the nuclear spins of the solvent, as it was suggested in [4,16]. Indeed, the water proton relativity of Gd@C82(OH)n has turned out to be 20 times higher than that of the commercial contrast agent magnevist (gadolinium-diethylenetri-aminepentaacetic acid) [18]. The idea of using EMF as contrast agents for MRI appears to have considerable promise. For example, the derivatives of Gd-EMF functionalized with special cytokines increase their selectivity to the markers of chronic post-traumatic osteomyelitis [19] while the additional amino-groups can allow to use the Gd-EMF in imaging the glioblastoma tumor cells [20]. Moreover, the noninvasive imaging approach to detect and clinically differentiate chronic post-traumatic osteomyelitis from aseptic inflammation using the targeted metallofullerene MRI probe has been developed [21]. Thus, there are the grounds to believe that EMF, due to their unique physical and chemical properties, can provide prospects for designing the novel relaxants for MRI as well as the effective pharmaceuticals for radiation medicine in the new millennium.

Summing up the fullerene trend in biomedicine, one should take into account that all fullerenes are the artificial compounds. As such, they are extraneous to the living Nature. Therefore, no wonder that fullerenes were proved to be, in a greater or lesser degree, toxic [2,22,23]. Meanwhile, favorable biological responses of cells and multi-cellular organisms to low-dose exposures to toxins have long been known. This is a well-known phenomenon, the so-called hormesis. As it was said by Paracelsus, all things are poison, and nothing is without poison, the dosage alone makes it, so a thing is not a poison [24]. Therefore, it is little wonder that some derivates of empty fullerenes as well as some derivates of endohedral metallofullerenes, when being used at the relevantly low doses, display the above-mentioned therapeutic effects. For example, the commercially available creams, based on the C60-fullerenes can be found on the market [25]. Yet, negative side effects of long-range using of such compounds can hardly be excluded.

In summary, it should be recognized that, in spite of all the exciting ideas of using fullerenes in biomedicine proposed in the last years, most of them have already lost their charm.

References

  1. Kroto HW, Heath JR, Brien SC, Curl RF, Smalley RE (1985) C-60-buckminsterfullerene. Nature 318(642): 161-163.
  2. Castro E, Hernandez GA, Zavala G, Echegoyen L (2017) Fullerenes in biology and medicine. J Mater Chem B 5: 6523-6535.
  3. Chai Y, Guo T, Jin C, Haufler RE, Chibante LPF, et al. (1991) Fullerenes with metals inside. J Phys Chem 95: 7564-7568.
  4. (a) Koltover VK (2007) Endohedral fullerenes: from chemical physics to nanotechnology and nanomedicine. In: Lang M (Eds.), Progress in Fullerene Research. Nova Science Publication, New York, pp. 199-233. (b) Koltover VK (2011) Paramagnetic endohedral fullerenes. In: Wythers MC (Eds.), Advances in materials science research, Nova Science Publishing, New York 1: 259-275.
  5. Cai X, Jia H, Liu Z, Hou B, Luo C, et al. (2008) Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+-induced cellular model of Parkinson's disease. J Neurosci Res 86(16): 3622-3634.
  6. Zhilenkov AV, Khakina EA, Troshin PA, Karimov IF, Deryabin DG (2019) Water-soluble anionic C60-fullerene derivatives as antidotes for Hg(II) ions in tests on Escherichia Coli Pharm Chem J 53: 312-317.
  7. Injac R, Perse M, Cerne M, Potocnik N, Radic N, et al. (2009) Protective effects of fullerenol C-60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer. Biomaterials 30: 1184-1196.
  8. Theriot CA, Casey RC, Moore VC, Strukelj B, Mitchell L, et al. (2010). Dendro [C60] fullerene DF-1 provides radioprotection to radiosensitive mammalian cells. Radiat Environ Biophys 49: 437-445.
  9. Gao J, Wang Y, Folta KM, Krishna V, Bai W, et al. (2011) Polyhydroxy fullerenes (fullerols or fullerenols): beneficial effects on growth and lifespan in diverse biological models. Plos One 6(5): 19976.
  10. Baati T, Bourasset F, Gharbi N, Njim L, Abderrabba M, et al. (2012) The prolongation of the lifespan of rats by repeated oral administration of [60] fullerene. Biomaterials 33(19): 4936-4946.
  11. Yablonskaya OI, Ryndina TS, Voeikov VL, Khokhlov AN (2013) A paradoxical effect of hydrated C60-fullerene at an ultralow concentration on the viability and aging of cultured Chinese hamster cells. Moscow Univ Bio Sci Bull 68: 63-68.
  12. Ngan CL, Basri M, Tripathy M, Karjiban RA, Abdul E (2015) Skin intervention of fullerene-integrated nano emulsion in structural and collagen regeneration against skin aging. Eur J Pharm Sci 70: 22-28.
  13. Galvan YuP, Alperovich I, Zolotukhin P, Prazdnova E, Mazanko M, et al. (2017) Fullerenes as anti-aging antioxidants. Current Aging Sci 10(1): 56-67.
  14. Soldatova Yu, Kotelnikova RA, Zhilenkov AV, Faingold, Troshin PA, et al. (2019) Potassium salt of fullerenylpenta-N- dihydroxytyrosine effects on type 2 diabetes mellitus therapeutic targets. Doklady Biochem 488(1): 338-341.
  15. Bobylev AG, Kraevayab OA, Bobyleva LG, Khakina EA, Fadeev RS, et al. (2019) Anti-amyloid activities of three different types of water-soluble fullerene derivatives. Colloids and Surfaces B: Biointerfaces 183(1): 110426.
  16. (a) Koltover VK, Kasumova LT (2002) Towards the novel metallofullerene-based probes for electron paramagnetic resonance, nuclear magnetic resonance and nuclear medicine. Indian J Chem Sec A 41A(1): 94-95. (b) Parnyuk TA, Koltover VK (2002) The potential bio-medical applications of fullerenes and endo metal lo fullerenes. Free Radic Biol Med 33(Suppl 1): S227-S228.
  17. Diener MD, Alford JM, Kennel SJ, Mirzadeh S (2007) 212Pb@C60 and its water-soluble derivatives: Synthesis, stability, and suitability for radioimmunotherapy. J Amer Chem Soc 129(16): 5131-5138.
  18. Mikawa M, Kato H, Okumura M, Narazaki M, Kanazawa Y, et al. (2001) Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents. Bioconjugate Chem 12(4): 510-514.
  19. Wang L, Zhu X, Tang X, Wu C, Zhou Z, et al. (2015) A multiple gadolinium complex decorated fullerene as a highly sensitive T-1 contrast agent. Chem Commun 51(21): 4390-4393.
  20. Li T, Murphy S, Kiselev B, Bakshi KS, Zhang J, et al. (2015) A new interleukin-13 amino-coated gadoliniumetallofullerene nanoparticle for targeted MRI detection of glioblastoma tumor cells. J Amer Chem Soc 137(24): 7881-7888.
  21. Xiao L, Li T, Ding M, Yang J, Rodriguez J, et al. (2017) Detecting chronic post-traumatic osteomyelitis of mouse tibia via an IL-13R alpha(2) targeted metallofullerene magnetic resonance imaging probe. Bioconjugate Chem 28(2): 649-658.
  22. Sayes CM, Fortner JD, Guo W, Lyon D, Boyd AM, et al. (2004) The differential cytotoxicity of water-soluble fullerenes. Nano Lett 4: 1881-1887.
  23. Fujita K, Morimoto Y, Endoh S, Uchida K, Fukui H, et al. (2010) Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C-60 fullerenes. Toxicology 274(1-3): 34-41.
  24. Calabrese EJ (2004) Hormesis: A revolution in toxicology, risk assessment and medicine. EMBO Rep 5(Suppl 1): S37-S40.
  25. Mousavi SZ, Nafisi S, Maibach HI (2017) Fullerene nanoparticle in dermatological and cosmetic applications. Nanomed Nanotech Biol Med 13(3): 1071-1087.

© 2019 Vitaly K Koltover. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.



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