Skip to main content
SpringerLink
Log in

A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Two-dimensional graphene and its composite nanomaterials offer interesting physical/chemical properties and have been extensively explored in a wide range of fields in recent years. In this work, we synthesize a multi-functional superparamagnetic graphene oxide-iron oxide hybrid nanocomposite (GO-IONP), which is then functionalized by a biocompatible polyethylene glycol (PEG) polymer to acquire high stability in physiological solutions. A chemotherapy drug, doxorubicin (DOX), was loaded onto GO-IONP-PEG, forming a GO-IONP-PEG-DOX complex, which enables magnetically targeted drug delivery. GO-IONP-PEG also exhibits strong optical absorbance from the visible to the near-infrared (NIR) region, and can be utilized for localized photothermal ablation of cancer cells guided by the magnetic field. Moreover, for the first time, in vivo magnetic resonance (MR) imaging of tumor-bearing mice is also demonstrated using GO-IONP-PEG as the T 2 contrast agent. Our work suggests the promise of using multifunctional GO-based nanocomposites for applications in cancer theranostics.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Novoselov, K. S.; Jiang, Z.; Zhang, Y.; Morozov, S. V.; Stormer, H. L.; Zeitler, U.; Maan, J. C.; Boebinger, G. S.; Kim, P.; Geim, A. K. Room-temperature quantum Hall effect in graphene. Science 2007, 315, 1379.

    Article  CAS  Google Scholar 

  2. Zhang, Y. B.; Tan, Y. W.; Stormer, H. L.; Kim, P. Experimental observation of the quantum Hall effect and Berry’s phase in graphene. Nature 2005, 438, 201–204.

    Article  CAS  Google Scholar 

  3. Balandin, A. A.; Ghosh, S.; Bao, W.; Calizo, I.; Teweldebrhan, D.; Miao, F.; Lau, C. N. Superior thermal conductivity of single-layer graphene. Nano Lett. 2008, 8, 902–907.

    Article  CAS  Google Scholar 

  4. Lee, C.; Wei, X.; Kysar, J. W.; Hone, J. Measurement of the elastic properties and intrinsic strength of monolayer graphene. Science 2008, 321, 385–388.

    Article  CAS  Google Scholar 

  5. Meyer, J. C.; Geim, A. K.; Katsnelson, M. I.; Novoselov, K. S.; Booth, T. J.; Roth, S. The structure of suspended graphene sheets. Nature 2007, 446, 60–63.

    Article  CAS  Google Scholar 

  6. Huang, X.; Yin, Z.; Wu, S.; Qi, X.; He, Q.; Zhang, Q.; Yan, Q.; Boey, F.; Zhang, H. Graphene-based materials: Synthesis, characterization, properties, and applications. Small 2011, 7, 1876–1902.

    Article  CAS  Google Scholar 

  7. Huang, X.; Qi, X.; Boey, F.; Zhang, H. Graphene-based composites. Chem. Soc. Rev. 2012, 41, 666–686.

    Article  CAS  Google Scholar 

  8. Liu, Z.; Robinson, J. T.; Sun, X.; Dai, H. PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 2008, 130, 10876–10877.

    Article  CAS  Google Scholar 

  9. Feng, L. Z.; Liu, Z. A. Graphene in biomedicine: Opportunities and challenges. Nanomedicine 2011, 6, 317–324.

    Article  CAS  Google Scholar 

  10. He, Q. Y.; Sudibya, H. G.; Yin, Z. Y.; Wu, S. X.; Li, H.; Boey, F.; Huang, W.; Chen, P.; Zhang, H. Centimeter-long and large-scale micropatterns of reduced graphene oxide films: Fabrication and sensing applications. ACS Nano 2010, 4, 3201–3208.

    Article  CAS  Google Scholar 

  11. Sudibya, H. G.; He, Q. Y.; Zhang, H.; Chen, P. Electrical detection of metal ions using field-effect transistors based on micropatterned reduced graphene oxide films. ACS Nano 2011, 5, 1990–1994.

    Article  CAS  Google Scholar 

  12. He, S.; Song, B.; Li, D.; Zhu, C.; Qi, W.; Wen, Y.; Wang, L.; Song, S.; Fang, H.; Fan, C. A graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis. Adv. Funct. Mater. 2010, 20, 453–459.

    Article  CAS  Google Scholar 

  13. Tang, L. A. L.; Wang, J.; Loh, K. P. Graphene-based SELDI probe with ultrahigh extraction and sensitivity for DNA oligomer. J. Am. Chem. Soc. 2010, 132, 10976–10977.

    Article  CAS  Google Scholar 

  14. Feng, L.; Zhang, S.; Liu, Z. Graphene based gene transfection. Nanoscale 2011, 3, 1252–1257.

    Article  CAS  Google Scholar 

  15. Zhang, L.; Xia, J.; Zhao, Q.; Liu, L.; Zhang, Z. Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small 2010, 6, 537–544.

    Article  CAS  Google Scholar 

  16. Yang, K.; Zhang, S.; Zhang, G.; Sun, X.; Lee, S. T.; Liu, Z. Graphene in mice: Ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 2010, 10, 3318–3323.

    Article  CAS  Google Scholar 

  17. Yin, Z.; He, Q.; Huang, X.; Zhang, J.; Wu, S.; Chen, P.; Lu, G.; Chen, P.; Zhang, Q.; Yan, Q.; Zhang, H. Real-time DNA detection using Pt nanoparticle-decorated reduced graphene oxide field-effect transistors. Nanoscale 2012, 4, 293–297.

    Article  CAS  Google Scholar 

  18. Wang, Z.; Zhang, J.; Chen, P.; Zhou, X.; Yang, Y.; Wu, S.; Niu, L.; Han, Y.; Wang, L.; Chen, P.; Boey, F.; Zhang, Q.; Liedberg, B.; Zhang, H. Label-free, electrochemical detection of methicillin-resistant Staphylococcus aureus DNA with reduced graphene oxide-modified electrodes. Biosens. Bioelectron. 2011, 26, 3881–3886.

    Article  CAS  Google Scholar 

  19. Wang, Z.; Zhou, X.; Zhang, J.; Boey, F.; Zhang, H. Direct electrochemical reduction of single-layer graphene oxide and subsequent functionalization with glucose oxidase. J. Phys. Chem. C 2009, 113, 14071–14075.

    Article  CAS  Google Scholar 

  20. Peng, C.; Jiang, B.; Liu, Q.; Guo, Z.; Xu, Z.; Huang, Q.; Xu, H.; Tai, R.; Fan, C. Graphene-templated formation of two-dimensional lepidocrocite nanostructures for high-efficiency catalytic degradation of phenols. Energy Environ. Sci. 2011, 4, 2035–2040.

    Article  CAS  Google Scholar 

  21. Tian, B.; Wang, C.; Zhang, S.; Feng, L. Z.; Liu, Z. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano 2011, 5, 7000–7009.

    Article  CAS  Google Scholar 

  22. Robinson, J. T.; Tabakman, S. M.; Liang, Y. Y.; Wang, H. L.; Casalongue, H. S.; Vinh, D.; Dai, H. J. Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. J. Am. Chem. Soc. 2011, 133, 6825–6831.

    Article  CAS  Google Scholar 

  23. Zhang, W.; Guo, Z. Y.; Huang, D. Q.; Liu, Z. M.; Guo, X.; Zhong, H. Q. Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. Biomaterials 2011, 32, 8555–8561.

    Article  CAS  Google Scholar 

  24. Markovic, Z. M.; Harhaji-Trajkovic, L. M.; Todorovic-Markovic, B. M.; Kepic, D. P.; Arsikin, K. M.; Jovanovic, S. P.; Pantovic, A. C.; Dramicanin, M. D.; Trajkovic, V. S. In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. Biomaterials 2011, 32, 1121–1129.

    Article  CAS  Google Scholar 

  25. Yang, K.; Wan, J.; Zhang, S.; Tian, B.; Zhang, Y.; Liu, Z. The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. Biomaterials, in press, 2012, DOI: 10.1016/j.biomaterials.2011.11.064.

  26. Zhang, Y. B.; Ali, S. F.; Dervishi, E.; Xu, Y.; Li, Z. R.; Casciano, D.; Biris, A. S. Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano 2010, 4, 3181–3186.

    Article  CAS  Google Scholar 

  27. Wang, K.; Ruan, J.; Song, H.; Zhang, J.; Wo, Y.; Guo, S.; Cui, D. Biocompatibility of graphene oxide. Nanoscale Res. Lett. 2011, 6, 8.

    Google Scholar 

  28. Duch, M. C.; Budinger, G. R. S.; Liang, Y. T.; Soberanes, S.; Urich, D.; Chiarella, S. E.; Campochiaro, L. A.; Gonzalez, A.; Chandel, N. S.; Hersam, M. C.; Mutlu, G. M. Minimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lung. Nano Lett. 2011, 11, 5201–5207.

    Article  Google Scholar 

  29. Sun, X.; Liu, Z.; Welsher, K.; Robinson, J. T.; Goodwin, A.; Zaric, S.; Dai, H. Nano-graphene oxide for cellular imaging and drug delivery. Nano Res. 2008, 1, 203–212.

    Article  CAS  Google Scholar 

  30. Yang, K.; Wan, J. M.; Zhang, S. A.; Zhang, Y. J.; Lee, S. T.; Liu, Z. A. In vivo pharmacokinetics, long-term biodistribution, and toxicology of PEGylated graphene in mice. ACS Nano 2011, 5, 516–522.

    Article  CAS  Google Scholar 

  31. Zhang, S. A.; Yang, K.; Feng, L. Z.; Liu, Z. In vitro and in vivo behaviors of dextran functionalized graphene. Carbon 2011, 49, 4040–4049.

    Article  CAS  Google Scholar 

  32. Agarwal, S.; Zhou, X.; Ye, F.; He, Q.; Chen, G. C. K.; Soo, J.; Boey, F.; Zhang, H.; Chen, P. Interfacing live cells with nanocarbon substrates. Langmuir 2010, 26, 2244–2247.

    Article  CAS  Google Scholar 

  33. Wang, H. L.; Liang, Y. Y.; Mirfakhrai, T.; Chen, Z.; Casalongue, H. S.; Dai, H. J. Advanced asymmetrical supercapacitors based on graphene hybrid materials. Nano Res. 2011, 4, 729–736.

    Article  CAS  Google Scholar 

  34. Wang, P.; Jiang, T. F.; Zhu, C. Z.; Zhai, Y. M.; Wang, D. J.; Dong, S. J. One-step, solvothermal synthesis of graphene-CdS and graphene-ZnS quantum dot nanocomposites and their interesting photovoltaic properties. Nano Res. 2010, 3, 794–799.

    Article  Google Scholar 

  35. Cao, X.; Shi, Y.; Shi, W.; Lu, G.; Huang, X.; Yan, Q.; Zhang, Q.; Zhang, H. Preparation of novel 3D graphene networks for supercapacitor applications. Small 2011, 7, 3163–3168.

    Article  CAS  Google Scholar 

  36. Xu, C.; Wang, X.; Zhu, J. Graphene-metal particle nano-composites. J. Phys. Chem. C 2008, 112, 19841–19845.

    Article  CAS  Google Scholar 

  37. Liang, Y. Y.; Wang, H. L.; Casalongue, H. S.; Chen, Z.; Dai, H. J. TiO2 nanocrystals grown on graphene as advanced photocatalytic hybrid materials. Nano Res. 2010, 3, 701–705.

    Article  CAS  Google Scholar 

  38. Shan, C.; Yang, H.; Song, J.; Han, D.; Ivaska, A.; Niu, L. Direct electrochemistry of glucose oxidase and biosensing for glucose based on graphene. Anal. Chem. 2009, 81, 2378–2382.

    Article  CAS  Google Scholar 

  39. Liang, J.; Xu, Y.; Sui, D.; Zhang, L.; Huang, Y.; Ma, Y.; Li, F.; Chen, Y. Flexible, magnetic, and electrically conductive graphene/Fe3O4 paper and its application for magnetic-controlled switches. J. Phys. Chem. C 2010, 114, 17465–17471.

    Article  CAS  Google Scholar 

  40. Zhou, G.; Wang, D. W.; Li, F.; Zhang, L.; Li, N.; Wu, Z. S.; Wen, L.; Lu, G. Q.; Cheng, H. M. Graphene-wrapped Fe3O4 anode material with improved reversible capacity and cyclic stability for lithium ion batteries. Chem. Mater. 2010, 22, 5306–5313.

    Article  CAS  Google Scholar 

  41. Cong, H. P.; He, J. J.; Lu, Y.; Yu, S. H. Water-soluble magnetic-functionalized reduced graphene oxide sheets: In situ synthesis and magnetic resonance imaging applications. Small 2010, 6, 169–173.

    Article  CAS  Google Scholar 

  42. Ji, L.; Tan, Z.; Kuykendall, T. R.; Aloni, S.; Xun, S.; Lin, E.; Battaglia, V.; Zhang, Y. Fe3O4 nanoparticle-integrated graphene sheets for high-performance half and full lithium ion cells. Phys. Chem. Chem. Phys. 2011, 13, 7170–7177.

    Article  CAS  Google Scholar 

  43. Chen, W.; Yi, P.; Zhang, Y.; Zhang, L.; Deng, Z.; Zhang, Z. Composites of aminodextran-coated Fe3O4 nanoparticles and graphene oxide for cellular magnetic resonance imaging. ACS Appl. Mater. Interf. 2011, 3, 4085–4091.

    Article  CAS  Google Scholar 

  44. Yang, X.; Zhang, X.; Ma, Y.; Huang, Y.; Wang, Y.; Chen, Y. Superparamagnetic graphene oxide-Fe3O4 nanoparticles hybrid for controlled targeted drug carriers. J. Mater. Chem. 2009, 19, 2710–2714.

    Article  CAS  Google Scholar 

  45. Sun, H.; Cao, L.; Lu, L. Magnetite/reduced graphene oxide nanocomposites: One step solvothermal synthesis and use as a novel platform for removal of dye pollutants. Nano Res. 2011, 4, 550–562.

    Article  CAS  Google Scholar 

  46. Wang, C.; Cheng, L.; Liu, Z. Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. Biomaterials 2011, 32, 1110–1120.

    Article  CAS  Google Scholar 

  47. Liu, Z.; Fan, A. C.; Rakhra, K.; Sherlock, S.; Goodwin, A.; Chen, X.; Yang, Q.; Felsher, D. W.; Dai, H. Supramolecular stacking of doxorubicin on carbon nanotubes for in vivo cancer therapy. Angew. Chem Int. Ed. 2009, 48, 7668–7672.

    Article  CAS  Google Scholar 

  48. Sherlock, S. P.; Dai, H. Multifunctional FeCo-graphitic carbon nanocrystals for combined imaging, drug delivery and tumor-specific photothermal therapy in mice. Nano Res. 2011, 4, 1248–1260.

    Article  CAS  Google Scholar 

  49. Na, H. B.; Song, I. C.; Hyeon, T. Inorganic nanoparticles for MRI contrast agents. Adv. Mater. 2009, 21, 2133–2148.

    Article  CAS  Google Scholar 

  50. Wang, L.; Neoh, K. G.; Kang, E. T.; Shuter, B.; Wang, S. C. Superparamagnetic hyperbranched polyglycerol-grafted Fe3O4 nanoparticles as a novel magnetic resonance imaging contrast agent: An in vitro assessment. Adv. Funct. Mater. 2009, 19, 2615–2622.

    Article  CAS  Google Scholar 

  51. Ai, H.; Flask, C.; Weinberg, B.; Shuai, X. T.; Pagel, M. D.; Farrell, D.; Duerk, J.; Gao, J. Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes. Adv. Mater. 2005, 17, 1949–1952.

    Article  CAS  Google Scholar 

  52. Liu, Z.; Sun, X. M.; Nakayama-Ratchford, N.; Dai, H. J. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 2007, 1, 50–56.

    Article  Google Scholar 

  53. Xu, H.; Cheng, L.; Wang, C.; Ma, X.; Li, Y.; Liu, Z. Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for multimodal imaging and magnetic targeted drug delivery. Biomaterials 2011, 32, 9364–9373.

    Article  CAS  Google Scholar 

  54. Veiseh, O.; Gunn, J. W.; Zhang, M. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv. Drug Deliv. Rev. 2010, 62, 284–304.

    Article  CAS  Google Scholar 

  55. Chertok, B.; Moffat, B. A.; David, A. E.; Yu, F.; Bergemann, C.; Ross, B. D.; Yang, V. C. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials 2008, 29, 487–496.

    Article  CAS  Google Scholar 

  56. Cheng, L.; Yang, K.; Li, Y.; Chen, J.; Wang, C.; Shao, M.; Lee, S. T.; Liu, Z. Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. Angew. Chem Int. Ed. 2011, 50, 7385–7390.

    Article  CAS  Google Scholar 

  57. Cheng, L.; Yang, K.; Li, Y.; Zeng, X.; Shao, M.; Lee, S. T.; Liu, Z. Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy. Biomaterials, in press, 2012, DOI: 10.1016/j.biomaterials.2011.11.069.

  58. Chertok, B.; David, A. E.; Yang, V. C. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration. Biomaterials 2010, 31, 6317–6324.

    Article  CAS  Google Scholar 

  59. Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A. Plasmonic photothermal therapy (PPTT) using gold nano-particles. Lasers Med. Sci. 2008, 23, 217–228.

    Article  Google Scholar 

  60. Liu, X.; Tao, H.; Yang, K.; Zhang, S.; Lee, S. T.; Liu, Z. Optimization of surface chemistry on single-walled carbon nanotubes for in vivo photothermal ablation of tumors. Biomaterials 2011, 32, 144–151.

    Article  Google Scholar 

  61. Robinson, J. T.; Welsher, K.; Tabakman, S. M.; Sherlock, S. P.; Wang, H. L.; Luong, R.; Dai, H. J. High performance in vivo near-IR (> 1 μm) imaging and photothermal cancer therapy with carbon nanotubes. Nano Res. 2010, 3, 779–793.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China

    Xinxing Ma, Yonggang Li & Liang Guo

  2. Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Soochow University, Suzhou, Jiangsu, 215123, China

    Xinxing Ma, Huiquan Tao, Kai Yang, Liangzhu Feng, Liang Cheng, Xiaoze Shi & Zhuang Liu

Authors
  1. Xinxing Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huiquan Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kai Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liangzhu Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoze Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yonggang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhuang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yonggang Li, Liang Guo or Zhuang Liu.

Additional information

These authors contributed equally to this work

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, X., Tao, H., Yang, K. et al. A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging. Nano Res. 5, 199–212 (2012). https://doi.org/10.1007/s12274-012-0200-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-012-0200-y

Keywords

Search

Navigation