Fullerenes as unique nanopharmaceuticals for disease treatment


As unique nanoparticles, fullerenes have attracted much attention due to their unparalleled physical, chemical and biological properties. Various functionalized fullerenes with -OH, -NH2, -COOH, and peptide modifications were developed. It summarized the biological activities of fullerenes derivatives in cancer therapy with high efficiency and low toxicity, as reactive oxygen species scavenger and lipid peroxidation inhibitor, to inhibit human immunodeficiency virus and to suppress bacteria and microbial at low concentration. In addition, the mechanism for fullerene to enter cells and biodistribution of fullerene in vivo was also discussed. This research focuses on the current understanding of fullerenes-based nanomaterials in the potential clinical application as well as biological mechanism of fullerenes and its derivatives in disease therapy.

This is a preview of subscription content, log in to check access.


  1. 1

    Kroto HW, Heath JR, O’Brien SC, Curl RF, Smalley RE. C60: Buckminsterfullerene. Nature, 1985, 318: 162–163

    CAS  Article  Google Scholar 

  2. 2

    Okumura M, Mikawa M, Yokawa T, Kanazawa Y, Kato H, Shinohara H. Evaluation of water-soluble metallofullerenes as MRI contrast agents. Acad Radiol, 2002, 9Suppl 2: S495–497

    Article  Google Scholar 

  3. 3

    Ding YY, Zhang ZY, Zhou PJ, Liu JC, Wang ZM, Zhao YL. Research and development of gadolinium loaded liquid scintillator for Daya Bay neutrino experiment. J Rare Earths, 2007, 25: 310–313

    Google Scholar 

  4. 4

    Bolskar RD, Benedetto AF, Husebo LO, Price RE, Jackson EF, Wallace S, Wilson LJ, Alford JM. First soluble M@C60 derivatives provide enhanced access to metallofullerenes and permit in vivo evaluation of Gd@C60[C(COOH)2]10 as a MRI contrast agent. J Am Chem Soc, 2003, 125: 5471–5478

    CAS  Article  Google Scholar 

  5. 5

    Qu L, Cao WB, Xing GM, Zhang J, Yuan H, Tang J, Cheng Y, Zhang B, Zhao YL, Lei H. Study of rare earth encapsulated carbon nanomolecules for biomedical uses. J Alloy Compd, 2006, 408/412: 400–404

    Article  Google Scholar 

  6. 6

    Xing GM, Yuan H, He R, Gao XY, Jing L, Zhao F, Chai ZF, Zhao YL. The strong MRI relaxivity of paramagnetic nanoparticles. J Phys Chem B, 2008, 112: 6288–6291

    CAS  Article  Google Scholar 

  7. 7

    Meng H, Xing G, Sun B, Zhao F, Lei H, Li W, Song Y, Chen Z, Yuan H, Wang X, Long J, Chen C, Liang X, Zhang N, Chai Z, Zhao Y. Potent angiogenesis inhibition by the particulate form of fullerene derivatives. Acs Nano, 2010, 4: 2773–2783

    CAS  Article  Google Scholar 

  8. 8

    Yin J-J, Lao F, Fu PP, Wamer WG, Zhao YL, Xing GM, Gao XY, Sun BY, Li XY, Wang PC, Chen CY, Liang X-J. Inhibition of tumor growth by endohedral metallofullerenol nanoparticles optimized as reactive oxygen species scavenger. Molecular Pharmacol, 2008, 74: 1132–1140

    CAS  Article  Google Scholar 

  9. 9

    Liang X-J, Meng H, Wang YZ, He HY, Meng J, Lu J, Wang PC, Zhao YL, Gao XY, Sun BY, Chen CY, Xing GM, Shen DW, Gottesman MM, Wu Y, Yin J-J, Jia L. Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis. Proc Natl Acad Sci, 2010, 107: 7449–7454

    CAS  Article  Google Scholar 

  10. 10

    Satoh M, Takayanagi I. Pharmacological studies on fullerene (C60), a novel carbon allotrope, and its derivatives. J Pharmacol Sci, 2006, 100: 513–518

    CAS  Article  Google Scholar 

  11. 11

    Chen CY, Xing GM, Wang JX, Zhao YL, Li B, Tang J, Jia G, Wang TC, Sun J, Xing L, Yuan H, Gao YX, Meng H, Chen Z, Zhao F, Chai ZF, Fang XH. Multi hydroxylated [Gd@C82(OH)(22)](n) nanoparticles: Antineoplastic activity of high efficiency and low toxicity. Nano Lett, 2005, 5: 2050–2057

    CAS  Article  Google Scholar 

  12. 12

    Wang JX, Chen CY, Li B, Yu HW, Zhao YL, Sun J, Li YF, Xing GM, Yuan H, Tang J, Chen Z, Meng H, Gao YX, Ye C, Chai ZF, Zhu CF, Ma BC, Fang XH, Wan LJ. Antioxidative function and biodistribution of [Gd@C82(OH)(22)](n) nanoparticles in tumor-bearing mice. Biochem Pharmacol, 2006, 71: 872–881

    CAS  Article  Google Scholar 

  13. 13

    Liu Y, Jiao F, Qiu Y, Li W, Lao F, Zhou GQ, Sun BY, Xing GM, Dong JQ, Zhao YL, Chai ZF, Chen CY. The effect of Gd@C82(OH)(22) nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-alpha mediated cellular immunity. Biomaterials, 2009, 30: 3934–3945

    CAS  Article  Google Scholar 

  14. 14

    Wang Y, Juan LV, Ma X, Wang D, Chang Y, Nie G, Jia L, Duan X, Liang XJ. Specific hemosiderin deposition in spleen induced by a low dose of cisplatin: Altered iron metabolism and its implication as an acute hemosiderin formation model. Curr Drug Metab, 2010, 11: 207–515

    Google Scholar 

  15. 15

    Liu Y, Jiao F, Qiu Y, Li W, Qu Y, Tian C, Li Y, Bai R, Lao F, Zhao Y, Chai ZF, Chen C. Immunostimulatory properties and enhanced TNF- alpha mediated cellular immunity for tumor therapy by C60(OH)20 nanoparticles. Nanotechnology, 2009, 20: 415102

    Article  Google Scholar 

  16. 16

    Zakharian TY, Seryshev A, Sitharaman B, Gilbert BE, Knight V, Wilson LJ. A fullerene-paclitaxel chemotherapeutic: Synthesis, characterization, and study of biological activity in tissue culture. J Am Chem Soc, 2005, 127: 12508–12509

    CAS  Article  Google Scholar 

  17. 17

    Partha R, Mitchell LR, Lyon JL, Joshi PP, Conyers JL. Buckysomes: Fullerene-based nanocarriers for hydrophobic molecule delivery. Acs Nano, 2008, 2: 1950–1958

    CAS  Article  Google Scholar 

  18. 18

    Chaudhuri P, Paraskar A, Soni S, Mashelkar RA, Sengupta S. Fullerenol-cytotoxic conjugates for cancer chemotherapy. Acs Nano, 2009, 3: 2505–2514

    CAS  Article  Google Scholar 

  19. 19

    Tabata Y, Murakami Y, Ikada Y. Photodynamic effect of polyethylene glycol-modified fullerene on tumor. Jpn J Cancer Res, 1997, 88: 1108–1116

    CAS  Google Scholar 

  20. 20

    Chaudhuri P, Harfouche R, Soni S, Hentschel DM, Sengupta S. Shape effect of carbon nanovectors on angiogenesis. Acs Nano, 2010, 4: 574–582

    CAS  Article  Google Scholar 

  21. 21

    Markovic Z, Trajkovic V. Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). Biomaterials, 2008, 29: 3561–3573

    CAS  Article  Google Scholar 

  22. 22

    Yin JJ, Lao F, Fu PP, Wamer WG, Zhao YL, Wang PC, Qiu Y, Sun BY, Xing GM, Dong JQ, Liang XJ, Chen CY. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials, 2009, 30: 611–621

    CAS  Article  Google Scholar 

  23. 23

    Lao F, Li W, Han D, Qu Y, Liu Y, Zhao YL, Chen CY. Fullerene derivatives protect endothelial cells against NO-induced damage. Nanotechnology, 2009, 20: 225103(9pp)

    Google Scholar 

  24. 24

    Corona-Morales AA, Castell A, Escobar A, Drucker-Colin R, Zhang L. Fullerene C60 and ascorbic acid protect cultured chromaffin cells against levodopa toxicity. J Neurosci Res, 2003, 71: 121–126

    CAS  Article  Google Scholar 

  25. 25

    Ryan JJ, Bateman HR, Stover A, Gomez G, Norton SK, Zhao W, Schwartz LB, Lenk R, Kepley CL. Fullerene nanomaterials inhibit the allergic response. J Immunol, 2007, 179: 665–672

    CAS  Google Scholar 

  26. 26

    Mirkov SM, Djordjevic AN, Andric NL, Andric SA, Kostic TS, Bogdanovic GM, Vojinovic-Miloradov MB, Kovacevic RZ. Nitric oxide-scavenging activity of polyhydroxylated fullerenol, C60(OH)24. Nitric Oxide, 2004, 11: 201–207

    CAS  Article  Google Scholar 

  27. 27

    Injac R, Radic N, Govedarica B, Perse M, Cerar A, Djordjevic A, Strukelj B. Acute doxorubicin pulmotoxicity in rats with malignant neoplasm is effectively treated with fullerenol C60(OH)24 through inhibition of oxidative stress. Pharmacol Rep, 2009, 61: 335–342

    CAS  Google Scholar 

  28. 28

    Bogdanovic V, Stankov K, Icevic I, Zikic D, Nikolic A, Solajic S, Djordjevic A, Bogdanovic G. Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line. J Radiat Res (Tokyo), 2008, 49: 321–327

    CAS  Article  Google Scholar 

  29. 29

    Trajkovic S, Dobric S, Jacevic V, Dragojevic-Simic V, Milovanovic Z, Dordevic A. Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats. Colloids Surf B Biointerfaces, 2007, 58: 39–43

    CAS  Article  Google Scholar 

  30. 30

    Gharbi N, Pressac M, Hadchouel M, Szwarc H, Wilson S, Moussa F. [60] Fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett, 2005, 5: 2578–2585

    CAS  Article  Google Scholar 

  31. 31

    Huang ST, Ho CS, Lin CM, Fang HW, Peng YX. Development and biological evaluation of C(60) fulleropyrrolidine-thalidomide dyad as a new anti-inflammation agent. Bioorg Med Chem, 2008, 16: 8619–8626

    CAS  Article  Google Scholar 

  32. 32

    Daroczi B, Kari G, McAleer MF, Wolf JC, Rodeck U, Dicker AP. In vivo radioprotection by the fullerene nanoparticle DF-1 as assessed in a zebrafish model. Clin Cancer Res, 2006, 12: 7086–7091

    CAS  Article  Google Scholar 

  33. 33

    Markovic Z, Todorovic-Markovic B, Kleut D, Nikolic N, Vranjes-Djuric S, Misirkic M, Vucicevic L, Janjetovic K, Isakovic A, Harhaji L, Babic-Stojic B, Dramicanin M, Trajkovic V. The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes. Biomaterials, 2007, 28: 5437–5448

    CAS  Article  Google Scholar 

  34. 34

    Mroz P, Pawlak A, Satti M, Lee H, Wharton T, Gali H, Sarna T, Hamblin MR. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism. Free Radic Biol Med, 2007, 43: 711–719

    CAS  Article  Google Scholar 

  35. 35

    Schinazi RF, Sijbesma R, Srdanov G, Hill CL, Wudl F. Synthesis and virucidal activity of a water-soluble, configurationally stable, derivatized C60 fullerene. Antimicrob Agents Chemother, 1993, 37: 1707–1710

    CAS  Google Scholar 

  36. 36

    Friedman SH, Ganapathi PS, Rubin Y, Kenyon GL. Optimizing the binding of fullerene inhibitors of the HIV-1 protease through predicted increases in hydrophobic desolvation. J Med Chem, 1998, 41: 2424–2429

    CAS  Article  Google Scholar 

  37. 37

    Friedman SH, DeCamp DL, Sijbesma RP, Srdanov G, Wudl F, Kenyon GL. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J Am Chem Soc, 1993, 115: 6506–6509

    CAS  Article  Google Scholar 

  38. 38

    Mashino T, Shimotohno K, Ikegami N, Nishikawa D, Okuda K, Takahashi K, Nakamura S, Mochizuki M. Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg Med Chem Lett, 2005, 15: 1107–1109

    CAS  Article  Google Scholar 

  39. 39

    Bosi S, Da Ros T, Spalluto G, Balzarini J, Prato M. Synthesis and anti-HIV properties of new water-soluble bis-functionalized[60] fullerene derivatives. Bioorg Med Chem Lett, 2003, 13: 4437–40

    CAS  Article  Google Scholar 

  40. 40

    Marchesan S, Da Ros T, Spalluto G, Balzarini J, Prato M. Anti-HIV properties of cationic fullerene derivatives. Bioorg Med Chem Lett, 2005, 15: 3615–3618

    CAS  Article  Google Scholar 

  41. 41

    Zhu Z, Schuster DI, Tuckerman ME. Molecular dynamics study of the connection between flap closing and binding of fullerene-based inhibitors of the HIV-1 protease. Biochemistry, 2003, 42: 1326–1333

    CAS  Article  Google Scholar 

  42. 42

    Lee VS, Nimmanpipug P, Aruksakunwong O, Promsri S, Sompornpisut P, Hannongbua S. Structural analysis of lead fullerene-based inhibitor bound to human immunodeficiency virus type 1 protease in solution from molecular dynamics simulations. J Mol Graph Model, 2007, 26: 558–570

    CAS  Article  Google Scholar 

  43. 43

    Pastorin G, Marchesan S, Hoebeke J, Da Ros T, Ehret-Sabatier L, Briand JP, Prato M, Bianco A. Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase. Org Biomol Chem, 2006, 4: 2556–2562

    CAS  Article  Google Scholar 

  44. 44

    Zarubaev V, Belousova I, Kiselev O, Piotrovsky L, Anfimov P, Krisko T, Muraviova T, Rylkov V, Starodubzev A, Sirotkin A. Photodynamic inactivation of influenza virus with fullerene C60 suspension in allantoic fluid. Photodiagn Photodyn Ther, 2007, 4: 31–35

    Article  Google Scholar 

  45. 45

    Kumar A, Menon SK. Fullerene derivatized s-triazine analogues as antimicrobial agents. Eur J Med Chem, 2009, 44: 2178–2183

    CAS  Article  Google Scholar 

  46. 46

    Kumar A, Patel G, Menon SK. Fullerene isoniazid conjugate—a tuberculostat with increased lipophilicity: Synthesis and evaluation of antimycobacterial activity. Chem Biol Drug Des, 2009, 73: 553–557

    CAS  Article  Google Scholar 

  47. 47

    Tsao N, Luh TY, Chou CK, Chang TY, Wu JJ, Liu CC, Lei HY. In vitro action of carboxyfullerene. J Antimicrob Chemother, 2002, 49: 641–649

    CAS  Article  Google Scholar 

  48. 48

    Tsao N, Kanakamma PP, Luh TY, Chou CK, Lei HY. Inhibition of Escherichia coli-induced meningitis by carboxyfullerence. Antimicrob Agents Chemother, 1999, 43: 2273–2277

    CAS  Google Scholar 

  49. 49

    Tsao N, Luh TY, Chou CK, Wu JJ, Lin YS, Lei HY. Inhibition of group A streptococcus infection by carboxyfullerene. Antimicrob Agents Chemother, 2001, 45: 1788–1793

    CAS  Article  Google Scholar 

  50. 50

    Pellarini F, Pantarotto D, Da Ros T, Giangaspero A, Tossi A, Prato M. A novel [60]fullerene amino acid for use in solid-phase peptide synthesis. Org Lett, 2001, 3: 1845–1848

    CAS  Article  Google Scholar 

  51. 51

    Pantarotto D, Bianco A, Pellarini F, Tossi A, Giangaspero A, Zelezetsky I, Briand JP, Prato M. Solid-phase synthesis of fullerene-peptides. J Am Chem Soc, 2002, 124: 12543–12549

    CAS  Article  Google Scholar 

  52. 52

    Cho M, Fortner JD, Hughes JB, Kim JH. Escherichia coli inactivation by water-soluble, ozonated C60 derivative: Kinetics and mechanisms. Environ Sci Technol, 2009, 43: 7410–7415

    CAS  Article  Google Scholar 

  53. 53

    Mashino T, Usui N, Okuda K, Hirota T, Mochizuki M. Respiratory chain inhibition by fullerene derivatives: Hydrogen peroxide production caused by fullerene derivatives and a respiratory chain system. Bioorg Med Chem, 2003, 11: 1433–1438

    CAS  Article  Google Scholar 

  54. 54

    Lyon DY, Brunet L, Hinkal GW, Wiesner MR, Alvarez PJ. Antibacterial activity of fullerene water suspensions (nC60) is not due to ROS-mediated damage. Nano Lett, 2008, 8: 1539–1543

    CAS  Article  Google Scholar 

  55. 55

    Bosi S, Da Ros T, Castellano S, Banfi E, Prato M. Antimycobacterial activity of ionic fullerene derivatives. Bioorg Med Chem Lett, 2000, 10: 1043–1045

    CAS  Article  Google Scholar 

  56. 56

    Bedrov D, Smith GD, Davande H, Li L. Passive transport of C60 fullerenes through a lipid membrane: A molecular dynamics simulation study. J Phys Chem B, 2008, 112: 2078–2084

    CAS  Article  Google Scholar 

  57. 57

    Qiao R, Roberts AP, Mount AS, Klaine SJ, Ke PC. Translocation of C60 and its derivatives across a lipid bilayer. Nano Lett, 2007, 7: 614–619

    CAS  Article  Google Scholar 

  58. 58

    Sayes CM, Gobin AM, Ausman KD, Mendez J, West JL, Colvin VL. Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials, 2005, 26: 7587–7595

    CAS  Article  Google Scholar 

  59. 59

    Li W, Chen CY, Ye C, Wei TT, Zhao YL, Lao F, Chen Z, Meng H, Gao YX, Yuan H, Xing GM, Zhao F, Chai ZF, Zhang XJ, Yang FY, Han D, Tang XH, Zhang YG. The translocation of Fullerenic nanoparticles into Iysosome via the pathway of clathrin-mediated endocytosis. Nanotechnology, 2008, 19: 145102(12pp)

    Google Scholar 

  60. 60

    Zhou GQ, Li YF, Liu Y, Ge CC, Li W, Li B, Gao YX, Chen CY. Subcellular distribution of polyhydroxylated metallofullerene of Gd@C82(OH)22 in different tissues of tumor-bearing mice. J Nanosci Nanotechnol, 2009, accepted

  61. 61

    Geisow M. Pathways of endocytosis. Nature, 1980, 288: 434–436

    CAS  Article  Google Scholar 

  62. 62

    Goldstein JL, Anderson RG, Brown MS. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature, 1979, 279: 679–685

    CAS  Article  Google Scholar 

  63. 63

    Yang J, Wang K, Driver J, Barron AR. The use of fullerene substituted phenylalanine amino acid as a passport for peptides through cell membranes. Org Biomol Chem, 2007, 5: 260–266

    CAS  Article  Google Scholar 

  64. 64

    Yamago S, Tokuyama H, Nakamura E, Kikuchi K, Kananishi S, Sueki K, Nakahara H, Enomoto S, Ambe F. In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol, 1995, 2: 385–389

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Xing-Jie Liang.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ma, H., Liang, X. Fullerenes as unique nanopharmaceuticals for disease treatment. Sci. China Chem. 53, 2233–2240 (2010). https://doi.org/10.1007/s11426-010-4118-5

Download citation


  • fullerene
  • nanoparticle
  • nanomedicine
  • clinical application
  • biological effect