Archives of Pharmacal Research

, Volume 37, Issue 1, pp 43–52 | Cite as

Carbon-based drug delivery carriers for cancer therapy

  • Dong-Jin Lim
  • Myeongbu Sim
  • Leeseul Oh
  • Kyunghee Lim
  • Hansoo ParkEmail author


In the search to improve anticancer therapies, several drug carriers, including carbon-based nanomaterials have been studied. Both liposomes and polymeric microspheres have been used in anticancer drugs. However, there remains an on-going need for better therapeutic materials that have good drug solubility, an ability to reduce systemic toxicity through specific-tumor targeting, and rapid clearance. In this regard, carbon allotropes such as graphene oxide (GOs), carbon nanotubes (CNTs), and nanodiamonds (NDs), have been investigated, as they possess sufficient surface-to-volume ratio, thermal conductivity, rigid structural properties capable of post-chemical modification, and excellent biocompatibility. This review is aimed at exploring these carbon-based nanomaterials for use as multifaceted cancer drug carriers and is intended to demonstrate that GOs, CNTs, and NDs are likely to improve chemotherapeutical strategy for cancers in either a sole or combinational manner.


Nanodiamonds Graphene oxide Carbon nanotube Drug delivery 



This research was supported by the Chung-Ang University Research Scholarship Grants in 2013.


  1. Balandin, A.A., S. Ghosh, W. Bao, I. Calizo, D. Teweldebrhan, F. Miao, and C.N. Lau. 2008. Superior thermal conductivity of single-layer graphene. Nano Letters 8: 902–907.PubMedCrossRefGoogle Scholar
  2. Bhirde, A.A., V. Patel, J. Gavard, G. Zhang, A.A. Sousa, A. Masedunskas, R.D. Leapman, R. Weigert, J.S. Gutkind, and J.F. Rusling. 2009. Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. ACS Nano 3: 307–316.PubMedCentralPubMedCrossRefGoogle Scholar
  3. Chen, M., E.D. Pierstorff, R. Lam, S.-Y. Li, H. Huang, E. Osawa, and D. Ho. 2009. Nanodiamond-mediated delivery of water-insoluble therapeutics. ACS Nano 3: 2016–2022.PubMedCrossRefGoogle Scholar
  4. Chow, E.K., X.-Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho. 2011. Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Science Translational Medicine 3: 73ra21.PubMedCrossRefGoogle Scholar
  5. Erickson, K., R. Erni, Z. Lee, N. Alem, W. Gannett, and A. Zettl. 2010. Determination of the local chemical structure of graphene oxide and reduced graphene oxide. Advanced Materials 22: 4467–4472.PubMedCrossRefGoogle Scholar
  6. Freitag, M. 2008. Graphene: Nanoelectronics goes flat out. Nature Nanotechnology 3: 455–457.PubMedCrossRefGoogle Scholar
  7. Geim, A.K., and K.S. Novoselov. 2007. The rise of graphene. Nature Materials 6: 183–191.PubMedCrossRefGoogle Scholar
  8. Georgakilas, V., K. Kordatos, M. Prato, D.M. Guldi, M. Holzinger, and A. Hirsch. 2002. Organic functionalization of carbon nanotubes. Journal of the American Chemical Society 124: 760–761.PubMedCrossRefGoogle Scholar
  9. Georgakilas, V., M. Otyepka, A.B. Bourlinos, V. Chandra, N. Kim, K.C. Kemp, P. Hobza, R. Zboril, and K.S. Kim. 2012. Functionalization of graphene: Covalent and non-covalent approaches, derivatives and applications. Chemical Reviews 112: 6156–6214.PubMedCrossRefGoogle Scholar
  10. Ghosh, S., S. Dutta, E. Gomes, D. Carroll, R. D’agostino, J. Olson, M. Guthold, and W.H. Gmeiner. 2009. Increased heating efficiency and selective thermal ablation of malignant tissue with DNA-encased multiwalled carbon nanotubes. ACS Nano 3: 2667–2673.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Haley, B., and E. Frenkel. 2008. Nanoparticles for drug delivery in cancer treatment. Urologic oncology 26: 57–64.PubMedCrossRefGoogle Scholar
  12. Heister, E., V. Neves, C. Tîlmaciu, K. Lipert, V.S. Beltrán, H.M. Coley, S.R.P. Silva, and J. Mcfadden. 2009. Triple functionalisation of single-walled carbon nanotubes with doxorubicin, a monoclonal antibody, and a fluorescent marker for targeted cancer therapy. Carbon 47: 2152–2160.CrossRefGoogle Scholar
  13. Hirsch, A. 2002. Functionalization of single-walled carbon nanotubes. Angewandte Chemie International Edition 41: 1853–1859.CrossRefGoogle Scholar
  14. Huang, H., E. Pierstorff, E. Osawa, and D. Ho. 2007. Active nanodiamond hydrogels for chemotherapeutic delivery. Nano Letters 7: 3305–3314.PubMedCrossRefGoogle Scholar
  15. Huang, L.C.L., and H.-C. Chang. 2004. Adsorption and immobilization of cytochrome c on nanodiamonds. Langmuir 20: 5879–5884.PubMedCrossRefGoogle Scholar
  16. Huang, P., C. Xu, J. Lin, C. Wang, X. Wang, C. Zhang, X. Zhou, S. Guo, and D. Cui. 2011. Folic acid-conjugated graphene oxide loaded with photosensitizers for targeting photodynamic therapy. Theranostics 1: 240–250.PubMedCentralPubMedCrossRefGoogle Scholar
  17. Ji, Z., G. Lin, Q. Lu, L. Meng, X. Shen, L. Dong, C. Fu, and X. Zhang. 2012. Targeted therapy of SMMC-7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system. Journal of Colloid and Interface Science 365: 143–149.PubMedCrossRefGoogle Scholar
  18. Klumpp, C., K. Kostarelos, M. Prato, and A. Bianco. 2006. Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochimica et Biophysica Acta 1758: 404–412.PubMedCrossRefGoogle Scholar
  19. Lam, R., M. Chen, E. Pierstorff, H. Huang, E. Osawa, and D. Ho. 2008. Nanodiamond-embedded microfilm devices for localized chemotherapeutic elution. ACS Nano 2: 2095–2102.PubMedCrossRefGoogle Scholar
  20. Lay, C.L., H.Q. Liu, H.R. Tan, and Y. Liu. 2010. Delivery of paclitaxel by physically loading onto poly(ethylene glycol) (PEG)-graft-carbon nanotubes for potent cancer therapeutics. Nanotechnology 21: 065101.PubMedCrossRefGoogle Scholar
  21. Lee, C., X. Wei, J.W. Kysar, and J. Hone. 2008. Measurement of the elastic properties and intrinsic strength of monolayer graphene. Science 321: 385–388.PubMedCrossRefGoogle Scholar
  22. Levi-Polyachenko, N.H., E.J. Merkel, B.T. Jones, D.L. Carroll, and J.H.T. Stewart. 2009. Rapid photothermal intracellular drug delivery using multiwalled carbon nanotubes. Molecular Pharmaceutics 6: 1092–1099.PubMedCrossRefGoogle Scholar
  23. Li, F., S.-J. Park, D. Ling, W. Park, J.Y. Han, K. Na, and K. Char. 2013. Hyaluronic acid-conjugated graphene oxide/photosensitizer nanohybrids for cancer targeted photodynamic therapy. Journal of Materials Chemistry B 1: 1678–1686.CrossRefGoogle Scholar
  24. Li, J., Y. Zhu, W. Li, X. Zhang, Y. Peng, and Q. Huang. 2010. Nanodiamonds as intracellular transporters of chemotherapeutic drug. Biomaterials 31: 8410–8418.PubMedCrossRefGoogle Scholar
  25. Liu, Z., C. Davis, W. Cai, L. He, X. Chen, and H. Dai. 2008a. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proceedings of the National Academy of Sciences 105: 1410–1415.CrossRefGoogle Scholar
  26. Liu, Z., A.C. Fan, K. Rakhra, S. Sherlock, A. Goodwin, X. Chen, Q. Yang, D.W. Felsher, and H. Dai. 2009. Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer therapy. Angewandte Chemie 48: 7668–7672.PubMedCentralPubMedGoogle Scholar
  27. Liu, Z., J.T. Robinson, X. Sun, and H. Dai. 2008b. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. Journal of the American Chemical Society 130: 10876–10877.PubMedCentralPubMedCrossRefGoogle Scholar
  28. Machado, B.F., and P. Serp. 2012. Graphene-based materials for catalysis. Catalysis Science and Technology 2: 54–75.CrossRefGoogle Scholar
  29. Markovic, Z.M., L.M. Harhaji-Trajkovic, B.M. Todorovic-Markovic, D.P. Kepic, K.M. Arsikin, S.P. Jovanovic, A.C. Pantovic, M.D. Dramicanin, and V.S. Trajkovic. 2011. In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. Biomaterials 32: 1121–1129.PubMedCrossRefGoogle Scholar
  30. Mochalin, V.N., O. Shenderova, D. Ho, and Y. Gogotsi. 2012. The properties and applications of nanodiamonds. Nature Nanotechnology 7: 11–23.CrossRefGoogle Scholar
  31. Moore, L., E.K.-H. Chow, E. Osawa, J.M. Bishop, and D. Ho. 2013. Diamond-lipid hybrids enhance chemotherapeutic tolerance and mediate tumor regression. Advanced Materials 25: 3532–3541.PubMedCrossRefGoogle Scholar
  32. Novoselov, K.S., A.K. Geim, S.V. Morozov, D. Jiang, Y. Zhang, S.V. Dubonos, I.V. Grigorieva, and A.A. Firsov. 2004. Electric field effect in atomically thin carbon films. Science 306: 666–669.PubMedCrossRefGoogle Scholar
  33. Oberlin, A., M. Endo, and T. Koyama. 1976. Filamentous growth of carbon through benzene decomposition. Journal of Crystal Growth 32: 335–349.CrossRefGoogle Scholar
  34. Pan, Y., H. Bao, N.G. Sahoo, T. Wu, and L. Li. 2011. Water-soluble poly(N-isopropylacrylamide)–graphene sheets synthesized via click chemistry for drug delivery. Advanced Functional Materials 21: 2754–2763.CrossRefGoogle Scholar
  35. Pentecost, A., S. Gour, V. Mochalin, I. Knoke, and Y. Gogotsi. 2010. Deaggregation of nanodiamond powders using salt- and sugar-assisted milling. ACS Applied Materials and Interfaces 2: 3289–3294.PubMedCrossRefGoogle Scholar
  36. Qin, X.C., Z.Y. Guo, Z.M. Liu, W. Zhang, M.M. Wan, and B.W. Yang. 2013. Folic acid-conjugated graphene oxide for cancer targeted chemo-photothermal therapy. Journal of Photochemistry and Photobiology B 120: 156–162.CrossRefGoogle Scholar
  37. Rana, V.K., M.-C. Choi, J.-Y. Kong, G.Y. Kim, M.J. Kim, S.-H. Kim, S. Mishra, R.P. Singh, and C.-S. Ha. 2011. Synthesis and drug-delivery behavior of chitosan-functionalized graphene oxide hybrid nanosheets. Macromolecular Materials and Engineering 296: 131–140.CrossRefGoogle Scholar
  38. Shao, Y., J. Wang, H. Wu, J. Liu, I.A. Aksay, and Y. Lin. 2010. Graphene based electrochemical sensors and biosensors: A review. Electroanalysis 22: 1027–1036.CrossRefGoogle Scholar
  39. Shenderova, O., A. Koscheev, N. Zaripov, I. Petrov, Y. Skryabin, P. Detkov, S. Turner, and G. Van Tendeloo. 2011. Surface chemistry and properties of ozone-purified detonation nanodiamonds. The Journal of Physical Chemistry C 115: 9827–9837.CrossRefGoogle Scholar
  40. Stankovich, S., D.A. Dikin, G.H. Dommett, K.M. Kohlhaas, E.J. Zimney, E.A. Stach, R.D. Piner, S.T. Nguyen, and R.S. Ruoff. 2006. Graphene-based composite materials. Nature 442: 282–286.PubMedCrossRefGoogle Scholar
  41. Stoller, M.D., S. Park, Y. Zhu, J. An, and R.S. Ruoff. 2008. Graphene-based ultracapacitors. Nano Letters 8: 3498–3502.PubMedCrossRefGoogle Scholar
  42. Terrones, M. 2003. Science and technology of the twenty-first century: Synthesis, properties, and applications of carbon nanotubes. Annual Review of Materials Research 33: 419–501.CrossRefGoogle Scholar
  43. Tian, B., C. Wang, S. Zhang, L. Feng, and Z. Liu. 2011. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano 5: 7000–7009.PubMedCrossRefGoogle Scholar
  44. Tisler, J., R. Reuter, A. Lämmle, F. Jelezko, G. Balasubramanian, P.R. Hemmer, F. Reinhard, and J. Wrachtrup. 2011. Highly efficient FRET from a single nitrogen-vacancy center in nanodiamonds to a single organic molecule. ACS Nano 5: 7893–7898.PubMedCrossRefGoogle Scholar
  45. Wang, A.Z., R. Langer, and O.C. Farokhzad. 2012. Nanoparticle delivery of cancer drugs. Annual Review of Medicine 63: 185–198.PubMedCrossRefGoogle Scholar
  46. Wang, C.H., Y.J. Huang, C.W. Chang, W.M. Hsu, and C.A. Peng. 2009. In vitro photothermal destruction of neuroblastoma cells using carbon nanotubes conjugated with GD2 monoclonal antibody. Nanotechnology 20: 315101.PubMedCrossRefGoogle Scholar
  47. Wang, Y., Z. Li, J. Wang, J. Li, and Y. Lin. 2011. Graphene and graphene oxide: Biofunctionalization and applications in biotechnology. Trends in Biotechnology 29: 205–212.PubMedCrossRefGoogle Scholar
  48. Wang, Z., C. Zhou, J. Xia, B. Via, Y. Xia, F. Zhang, Y. Li, and L. Xia. 2013. Fabrication and characterization of a triple functionalization of graphene oxide with Fe3O4, folic acid and doxorubicin as dual-targeted drug nanocarrier. Colloids and Surfaces B 106: 60–65.CrossRefGoogle Scholar
  49. Webster, D.M., P. Sundaram, and M.E. Byrne. 2013. Injectable nanomaterials for drug delivery: carriers, targeting moieties, and therapeutics. European Journal of Pharmaceutics and Biopharmaceutics 84: 1–20.PubMedCrossRefGoogle Scholar
  50. Yang, K., J. Wan, S. Zhang, Y. Zhang, S.-T. Lee, and Z. Liu. 2010a. In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. ACS Nano 5: 516–522.PubMedCrossRefGoogle Scholar
  51. Yang, K., S. Zhang, G. Zhang, X. Sun, S.-T. Lee, and Z. Liu. 2010b. Graphene in mice: Ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Letters 10: 3318–3323.PubMedCrossRefGoogle Scholar
  52. Yang, Y., J. Wang, J. Zhang, J. Liu, X. Yang, and H. Zhao. 2009. Exfoliated graphite oxide decorated by PDMAEMA chains and polymer particles. Langmuir 25: 11808–11814.PubMedCrossRefGoogle Scholar
  53. Zhang, L., J. Xia, Q. Zhao, L. Liu, and Z. Zhang. 2010. Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small 6: 537–544.PubMedCrossRefGoogle Scholar
  54. Zhang, W., Z. Guo, D. Huang, Z. Liu, X. Guo, and H. Zhong. 2011a. Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. Biomaterials 32: 8555–8561.PubMedCrossRefGoogle Scholar
  55. Zhang, X.-Q., M. Chen, R. Lam, X. Xu, E. Osawa, and D. Ho. 2009a. Polymer-functionalized nanodiamond platforms as vehicles for gene delivery. ACS Nano 3: 2609–2616.PubMedCrossRefGoogle Scholar
  56. Zhang, X., L. Meng, Q. Lu, Z. Fei, and P.J. Dyson. 2009b. Targeted delivery and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes. Biomaterials 30: 6041–6047.PubMedCrossRefGoogle Scholar
  57. Zhang, X.Q., R. Lam, X. Xu, E.K. Chow, H.J. Kim, and D. Ho. 2011b. Multimodal nanodiamond drug delivery carriers for selective targeting, imaging, and enhanced chemotherapeutic efficacy. Advanced Materials 23: 4770–4775.PubMedCrossRefGoogle Scholar
  58. Zhu, S., J. Li, Y. Chen, Z. Chen, C. Chen, Y. Li, Z. Cui, and D. Zhang. 2012. Grafting of graphene oxide with stimuli-responsive polymers by using ATRP for drug release. Journal of Nanoparticle Research 14: 1–11.Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2013

Authors and Affiliations

  • Dong-Jin Lim
    • 1
  • Myeongbu Sim
    • 3
  • Leeseul Oh
    • 2
  • Kyunghee Lim
    • 2
  • Hansoo Park
    • 3
    Email author
  1. 1.Department of Biomedical EngineeringUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.School of Chemical EngineeringChung-Ang UniversitySeoulKorea
  3. 3.School of Integrative EngineeringChung-Ang UniversitySeoulKorea

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