Nanomedicine: Nanotechnology, Biology and Medicine
Volume 8, Issue 2 , Pages 136-146 , February 2012

Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells

  • Huan Meng, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • These authors contributed equally to this work.
    • ,
  • Gengmei Xing, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • These authors contributed equally to this work.
    • ,
  • Elvin Blanco, PhD

      Affiliations

    • Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA
    • ,
  • Yan Song, BS

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Lina Zhao, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Baoyun Sun, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Xiaoda Li, MS

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Paul C. Wang, PhD

      Affiliations

    • Laboratory of Molecular Imaging, Department of Radiology, Howard University, Washington, DC, USA
    • ,
  • Alexandru Korotcov, PhD

      Affiliations

    • Laboratory of Molecular Imaging, Department of Radiology, Howard University, Washington, DC, USA
    • ,
  • Wei Li, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Xing-Jie Liang, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Chunying Chen, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Hui Yuan, MS

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Feng Zhao, MS

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Zhen Chen, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Tong Sun, MS

      Affiliations

    • Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA
    • ,
  • Zhifang Chai, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • ,
  • Mauro Ferrari, PhD

      Affiliations

    • Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA
    • ,
  • Yuliang Zhao, PhD

      Affiliations

    • CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing 100049, and National Center for Nanosciences and Technology of China, Beijing China
    • Research Center for Cancer Nanotechnology, Tianjin Cancer Hospital and Chinese Academy of Sciences, Tianjin, China
    • Corresponding Author InformationCorresponding author: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, and National Center for Nanosciences and Technology of China, Beijing, China.

Received 10 May 2011 ,Accepted 28 August 2011.

References 

  1. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;106:161–171
  2. Qian X, Peng XH, Ansari DO, Yin-Goen Q, Chen GZ, Shin DM, et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol. 2008;26:83–90
  3. Stoeva SI, Lee JS, Smith JE, Rosen ST, Mirkin CA. Multiplexed detection of protein cancer markers with biobarcoded nanoparticle probes. J Am Chem Soc. 2006;128:8378–8379
  4. Zheng G, Patolsky F, Cui Y, Wang WU, Lieber CM. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol. 2005;23:1294–1301
  5. Chen C, Xing G, Wang J, Zhao Y, Li B, Tang J, et al. Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity. Nano Lett. 2005;5:2050–2057
  6. Liu Z, Cai W, He L, Nakayama N, Chen K, Sun X, et al. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat Nanotechnol. 2007;2:47–52
  7. Liu Z, Davis C, Cai W, He L, Chen X, Dai H. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc Natl Acad Sci U S A. 2008;105:1410–1415
  8. Liang XJ, Meng H, Wang Y, He H, Meng J, Lu J, et al. Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis. Proc Natl Acad Sci U S A. 2010;107:7449–7454
  9. Xing G, Yuan H, He R, Gao X, Jing L, Zhao F, et al. The strong MRI relaxivity of paramagnetic nanoparticles. J Phys Chem B. 2008;112:6288–6291
  10. Shu CY, Wang CR, Zhang JF, Gibson HW, Dorn HC, Corwin FD, et al. Organophosphonate functionalized Gd@C82 as a magnetic resonance imaging contrast agent. Chem Mater. 2008;20:2106–2109
  11. Mikawa M, Kato H, Okumura M, Narazaki M, Kanazawa Y, Miwa N, et al. Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents. Bioconjug Chem. 2001;12:510–514
  12. Meng H, Xing G, Sun B, Zhao F, Lei H, Li W, et al. Potent angiogenesis inhibition by the particulate form of fullerene derivatives. ACS Nano. 2010;4:2773–2783
  13. Liu Y, Jiao F, Qiu Y, Li W, Lao F, Zhou G, et al. The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-α mediated cellular immunity. Biomaterials. 2009;30:3934–3945
  14. Wang J, Chen C, Li B, Yu H, Zhao Y, Sun J, et al. Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice. Biochem Pharmacol. 2006;71:872–881
  15. Yin JJ, Lao F, Meng J, Fu PP, Zhao Y, Xing G, et al. Inhibition of tumor growth by endohedral metallofullerenol nanoparticles optimized as reactive oxygen species scavenger. Mol Pharmacol. 2008;74:1132–1140
  16. Yin D, Ge Z, Yang W, Liu C, Yuan Y. Inhibition of tumor metastasis in vivo by combination of paclitaxel and hyaluronic acid. Cancer Lett. 2006;243:71–79
  17. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  18. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64:327–336
  19. Dvorak HF, Senger DR, Dvorak AM. Fibrin as a component of the tumor stroma: origins and biological significance. Cancer Metastasis Rev. 1983;2:41–73
  20. Tlsty TD, Coussens LM. Tumor stroma and regulation of cancer development. Annu Rev Pathol. 2006;1:119–150
  21. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006;66:605–612
  22. Tang J, Xing G, Yuan H, Cao W, Jing L, Gao X, et al. Tuning electronic properties of metallic atom in bondage to a nanospace. J Phys Chem B. 2005;109:8779–8785
  23. Tang J, Xing G, Zhao F, Yuan H, Zhao Y. Modulation of structural and electronic properties of fullerene and metallofullerenes by surface chemical modifications. J Nanosci Nanotechnol. 2007;7:1085–1101
  24. Tang J, Xing G, Zhao Y, Jing L, Gao X, Cheng Y, et al. Periodical variation of electronic properties in polyhydroxylated metallofullerene materials. Adv Mater. 2006;18:1458–1462
  25. Li Y, Shen F, Liu B, Cheng G. Resveratrol inhibits matrix metalloproteinase-9 transcription in U937 cells. Acta Pharmacol Sin. 2003;24:1167–1171
  26. Liu WH, Chang LS. Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway. J Cell Physiol. 2010;224:775–785
  27. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–174
  28. Richert M, Phadke P, Matters G, DiGirolamo D, Washington S, Demers L, et al. Metastasis of hormone-independent breast cancer to lung and bone is decreased by alpha-difluoromethylornithine treatment. Breast Cancer Res. 2005;7:R819–R827
  29. Ran S, Mohamedali KA, Luster TA, Thorpe PE, Rosenblum MG. The vascular-ablative agent VEGF121/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors. Neoplasia. 2005;7:486–496
  30. Merck Manual Online. Breast cancer. Whitehouse Station, NJ: Merck Sharp & Dohme [updated 2008 Nov]. Available from: http://www.merck.com/mmpe/print/sec18/ch253/ch253e.html.
  31. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer—trials and tribulations. Science. 2002;295:2387–2392
  32. Mannello F. Natural bio-drugs as matrix metalloproteinase inhibitors: new perspectives on the horizon. Recent Pat Anticancer Drug Discov. 2006;1:91–103
  33. Sierevogel MJ, Velema E, van der Meer FJ, Nijhuis MO, Smeets M, de Kleijn DP, et al. Matrix metalloproteinase inhibition reduces adventitial thickening and collagen accumulation following balloon dilation. Cardiovasc Res. 2002;55:864–869
  34. Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001;193:727–740
  35. Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196:254–265
  36. Yamada KM. Cell biology: tumour jailbreak. Nature. 2003;424:889–890
  37. Hotary KB, Allen ED, Brooks PC, Datta NS, Long MW, Weiss SJ, et al. matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell. 2003;114:33–45
  38. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul. 2001;41:189–207

 The authors thank for the support of MOST 973 program (2009CB930204, 2011CB933403, 2010CB934000, 2012CB934000) and CAS Knowledge Innovation Program. This study was partly funded by National Natural Science Foundation of China (10875136), and U.S NIH/RCMI/NCRR (2G12RR003048) and DOD (W81XWH-10-1-0767). M.F., T.S., E.B., are grateful for the support of the U.S. DoD Innovator Award (W81XWH-09-1-0212), NIH U54CA143837 and U54CA151668, and the Ernest Cockrell Jr. Distinguished Endowed Chair.

PII: S1549-9634(11)00356-X

doi: 10.1016/j.nano.2011.08.019

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 8, Issue 2 , Pages 136-146 , February 2012

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