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Multifunctional FeCo-graphitic carbon nanocrystals for combined imaging, drug delivery and tumor-specific photothermal therapy in mice

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Abstract

Ultrasmall FeCo-graphitic carbon shell nanocrystals (FeCo/GC) are promising multifunctional materials capable of highly efficient drug delivery in vitro and magnetic resonance imaging in vivo. In this work, we demonstrate the use of FeCo/GC for highly effective cancer therapy through combined drug delivery, tumor-selective near-infrared photothermal therapy, and cancer imaging of a 4T1 syngeneic breast cancer model. The graphitic carbon shell of the ∼4 nm FeCo/GC readily loads doxorubicin (DOX) via π-π stacking and absorbs near-infrared light giving photothermal heating. When used for cancer treatment, intravenously administrated FeCo/GC-DOX led to complete tumor regression in 45% of mice when combined with 20 min of near-infrared laser irradiation selectively heating the tumor to 43–45 °C. In addition, the use of FeCo/GC-DOX results in reduced systemic toxicity compared with free DOX and appears to be safe in mice monitored for over 1 yr. FeCo/GC-DOX is shown to be a highly integrated nanoparticle system for synergistic cancer therapy leading to tumor regression of a highly aggressive tumor model.

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References

  1. Dewhirst, M. W. Future directions in hyperthermia biology. Int. J. Hyperthermia 1994, 10, 339–345.

    Article  CAS  Google Scholar 

  2. Falk, M. H.; Issels, R. D. Hyperthermia in oncology. Int. J. Hyperthermia 2001, 17, 1–18.

    Article  CAS  Google Scholar 

  3. Hahn, G. M.; Braun, J.; Harkedar, I. Thermochemotherapy: Synergism between hyperthermia (42–43°C) and adriamycin (or bleomycin) in mammalian cell inactivation. Proc. Natl. Acad. Sci. U. S. A. 1975, 72, 937–940.

    Article  CAS  Google Scholar 

  4. Hildebrandt, B.; Wust, P.; Ahlers, O.; Dieing, A.; Sreenivasa, G.; Kerner, T.; Felix, R.; Riess, H. The cellular and molecular basis of hyperthermia. Crit. Rev. Oncol. Hematolo 2002, 43, 33–56.

    Article  Google Scholar 

  5. Wust, P.; Hildebrandt, B.; Sreenivasa, G.; Rau, B.; Gellermann, J.; Riess, H.; Felix, R.; Schlag, P. M. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002, 3, 487–497.

    Article  CAS  Google Scholar 

  6. Vertrees, R. A.; Jordan, J. M.; Zwischenberger, J. B. Hyperthermia and chemotherapy: The science. In Current Clinical Oncology: Intraperitoneal Cancer Therapy, Helm, C. W.; Edwards, R. P., Eds.; Humana Press Inc.: Totowa, NJ, 2007; pp 71–100.

    Chapter  Google Scholar 

  7. Helm, C. W.; Edwards, R. P. Current Clinical Oncology: Intraperitoneal Cancer Therapy; Humana Press Inc.: Totowa, NJ, 2007.

    Book  Google Scholar 

  8. Hildebrandt, B.; Wust, P. The biologic rationale of hyperthermia. Cancer Treat. Res. 2007, 134, 171–184.

    CAS  Google Scholar 

  9. Purushotham, S.; Chang, P. E. J.; Rumpel, H.; Kee, I. H. C.; Ng, R. T. H.; Chow, P. K. H.; Tan, C. K.; Ramanujan, R. V. Thermoresponsive core-shell magnetic nanoparticles for combined modalities of cancer therapy. Nanotechnology 2009, 20, 305101.

    Article  CAS  Google Scholar 

  10. Power, S.; Slattery, M. M.; Lee, M. J. Nanotechnology and its relationship to interventional radiology. Part II: Drug delivery, thermotherapy, and vascular intervention. Cardiovasc. Intervent. Radiol. 2011, 34, 676–690.

    Article  Google Scholar 

  11. Park, J. H.; von Maltzahn, G.; Ong, L. L.; Centrone, A.; Hatton, T. A.; Ruoslahti, E.; Bhatia, S. N.; Sailor, M. J. Cooperative nanoparticles for tumor detection and photo-thermally triggered drug delivery. Adv. Mater. 2010, 22, 880–885.

    Article  CAS  Google Scholar 

  12. Park, J. H.; von Maltzahn, G.; Xu, M. J.; Fogal, V.; Kotamraju, V. R.; Ruoslahti, E.; Bhatia, S. N.; Sailor, M. J. Cooperative nanomaterial system to sensitize, target, and treat tumors. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 981–986.

    Article  CAS  Google Scholar 

  13. Robinson, J. T.; Welsher, K.; Tabakman, S. M.; Sherlock, S. P.; Wang, H.; 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 

  14. Lee, S. M.; Park, H.; Yoo, K. H. Synergistic cancer therapeutic effects of locally delivered drug and heat using multifunctional nanoparticles. Adv. Mater. 2010, 22, 4049–4053.

    Article  CAS  Google Scholar 

  15. Park, H.; Yang, J.; Lee, J.; Haam, S.; Choi, I. H.; Yoo, K. H. Multifunctional nanoparticles for combined doxorubicin and photothermal treatments. ACS Nano 2009, 3, 2919–2926.

    Article  CAS  Google Scholar 

  16. Park, H.; Yang, J.; Seo, S.; Kim, K.; Suh, J.; Kim, D.; Haam, S.; Yoo, K. H. Multifunctional nanoparticles for photo-thermally controlled drug delivery and magnetic resonance imaging enhancement. Small 2008, 4, 192–196.

    Article  CAS  Google Scholar 

  17. Lee, J. H.; Sherlock, S. P.; Terashima, M.; Kosuge, H.; Suzuki, Y.; Goodwin, A.; Robinson, J.; Seo, W. S.; Liu, Z.; Luong, R. et al. High-contrast in vivo visualization of microvessels using novel FeCo/GC magnetic nanocrystals. Magn. Reson. Med. 2009, 62, 1497–1509.

    Article  Google Scholar 

  18. Seo, W. S.; Lee, J. H.; Sun, X. M.; Suzuki, Y.; Mann, D.; Liu, Z.; Terashima, M.; Yang, P. C.; McConnell, M. V.; Nishimura, D. G. et al. FeCo/graphitic-shell nanocrystals as advanced magnetic-resonance-imaging and near-infrared agents. Nat. Mater. 2006, 5, 971–976.

    Article  CAS  Google Scholar 

  19. Sherlock, S. P.; Tabakman, S. M.; Xie, L. M.; Dai, H. J. Photothermally enhanced drug delivery by ultrasmall multifunctional FeCo/graphitic shell nanocrystals. ACS Nano 2011, 5, 1505–1512.

    Article  CAS  Google Scholar 

  20. Bausero, M. A.; Page, D. T.; Osinaga, E.; Asea, A. Surface expression of Hsp25 and Hsp72 differentially regulates tumor growth and metastasis. Tumor Biol. 2004, 25, 243–251.

    Article  CAS  Google Scholar 

  21. Working, P. K.; Dayan, A. D. Pharmacological-toxicological expert report: CAELYX. (Stealth liposomal doxorubicin HCl). Hum. Exp. Toxicol. 1996, 15, 751–785.

    CAS  Google Scholar 

  22. Seymour, L. W.; Ulbrich, K.; Strohalm, J.; Kopecek, J.; Duncan, R. The pharmacokinetics of polymer-bound adriamycin. Biochem. Pharmacol. 1990, 39, 1125–1131.

    Article  CAS  Google Scholar 

  23. Liu, D. L.; Andersson-Engels, S.; Sturesson, C.; Svanberg, K.; Hakansson, C. H.; Svanberg, S. Tumour vessel damage resulting from laser-induced hyperthermia alone and in combination with photodynamic therapy. Cancer Lett. 1997, 111, 157–165.

    Article  CAS  Google Scholar 

  24. Liu, P.; Zhang, A.; Xu, Y.; Xu, L. X. Study of non-uniform nanoparticle liposome extravasation in tumour. Int. J. Hyperthermia 2005, 21, 259–270.

    Article  CAS  Google Scholar 

  25. Lu, D.; Wientjes, M. G.; Lu, Z.; Au, J. L. Tumor priming enhances delivery and efficacy of nanomedicines. J. Pharmacol. Exp. Ther. 2007, 322, 80–88.

    Article  CAS  Google Scholar 

  26. Kosuge, H.; Sherlock, S. P.; Kitagawa, T.; Terashima, M.; Barral, J. K.; Nishimura, D. G.; Dai, H. J.; McConnell, M. V. FeCo/graphite nanocrystals for multi-modality imaging of experimental vascular inflammation. PLoS One 2011, 6, e14523.

    Article  CAS  Google Scholar 

  27. Liu, Z.; Chen, K.; Davis, C.; Sherlock, S.; Cao, Q. Z.; Chen, X. Y.; Dai, H. J. Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res. 2008, 68, 6652–6660.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, Stanford University, Stanford, CA, 94305, USA

    Sarah P. Sherlock & Hongjie Dai

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  1. Sarah P. Sherlock
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  2. Hongjie Dai
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Correspondence to Hongjie Dai.

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Sherlock, S.P., Dai, H. Multifunctional FeCo-graphitic carbon nanocrystals for combined imaging, drug delivery and tumor-specific photothermal therapy in mice. Nano Res. 4, 1248–1260 (2011). https://doi.org/10.1007/s12274-011-0176-z

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  • DOI: https://doi.org/10.1007/s12274-011-0176-z

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