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Nano Research

, Volume 11, Issue 9, pp 4890–4904 | Cite as

General synthesis of silica-based yolk/shell hybrid nanomaterials and in vivo tumor vasculature targeting

  • Feng Chen
  • Shreya Goel
  • Sixiang Shi
  • Todd E. Barnhart
  • Xiaoli Lan
  • Weibo Cai
Research Article

Abstract

Multifunctional yolk/shell-structured hybrid nanomaterials have attracted increasing interest as theranostic nanoplatforms for cancer imaging and therapy. However, because of the lack of suitable surface engineering and tumor targeting strategies, previous research has focused mainly on nanostructure design and synthesis with few successful examples showing active tumor targeting after systemic administration. In this study, we report the general synthetic strategy of chelator-free zirconium-89 (89Zr)-radiolabeled, TRC105 antibody-conjugated, silica-based yolk/shell hybrid nanoparticles for in vivo tumor vasculature targeting. Three types of inorganic nanoparticles with varying morphologies and sizes were selected as the internal cores, which were encapsulated into single hollow mesoporous silica nanoshells to form the yolk/shell-structured hybrid nanoparticles. As a proof-of-concept, we demonstrated successful surface functionalization of the nanoparticles with polyethylene glycol, TRC105 antibody (specific for CD105/endoglin), and 89Zr (a positron-emitting radioisotope), and enhanced in vivo tumor vasculature-targeted positron emission tomography imaging in 4T1 murine breast tumor-bearing mice. This strategy could be applied to the synthesis of other types of yolk/shell theranostic nanoparticles for tumor-targeted imaging and drug delivery.

Keywords

yolk/shell intrinsic radiolabeling vasculature targeting positron emission tomography zirconium-89 

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Notes

Acknowledgements

This work is supported, in part, by the University of Wisconsin-Madison, the National Institutes of Health (P30CA014520 and NIBIB/NCI 1R01CA169365), the National Natural Science Foundation of China (No. 81630049), and the American Cancer Society (No. 125246-RSG-13-099-01-CCE).

Supplementary material

12274_2018_2078_MOESM1_ESM.pdf (1.3 mb)
General synthesis of silica-based yolk/shell hybrid nanomaterials and in vivo tumor vasculature targeting

References

  1. [1]
    Ledford, H. Bankruptcy filing worries developers of nanoparticle cancer drugs. Nature 2016, 533, 304–305.CrossRefGoogle Scholar
  2. [2]
    Shi, J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer 2017, 17, 20–37.CrossRefGoogle Scholar
  3. [3]
    Hare, J. I.; Lammers, T.; Ashford, M. B.; Puri, S.; Storm, G.; Barry, S. T. Challenges and strategies in anti-cancer nanomedicine development: An industry perspective. Adv. Drug Deliv. Rev. 2017, 108, 25–38.CrossRefGoogle Scholar
  4. [4]
    Davis, M. E.; Chen, Z.; Shin, D. M. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat. Rev. Drug Discov. 2008, 7, 771–782.CrossRefGoogle Scholar
  5. [5]
    Chen, H. M.; Zhang, W. Z.; Zhu, G. Z.; Xie, J.; Chen, X. Y. Rethinking cancer nanotheranostics. Nat. Rev. Mater. 2017, 2, 17024.CrossRefGoogle Scholar
  6. [6]
    Bradbury, M. S.; Pauliah, M.; Zanzonico, P.; Wiesner, U.; Patel, 5. Intraoperative mapping of sentinel lymph node metastases using a clinically translated ultrasmall silica nanoparticle. Wiley Interdiscip. Rev. Nanomed Nanobiotechnol. 2016, 8, 535–553.CrossRefGoogle Scholar
  7. [7]
    Croissant, J. G.; Fatieiev, Y.; Khashab, N. M. Degradability and clearance of silicon, organosilica, silsesquioxane, silica mixed oxide, and mesoporous silica nanoparticles. Adv. Mater. 2017, 29, 1604634.CrossRefGoogle Scholar
  8. [8]
    Purbia, R.; Paria, S. Yolk/shell nanoparticles: Classifications, synthesis, properties, and applications. Nanoscale 2015, 7, 19789–19873.CrossRefGoogle Scholar
  9. [9]
    Piao, Y. Z.; Burns, A.; Kim, J.; Wiesner, U.; Hyeon, T. Designed fabrication of silica-based nanostructured particle systems for nanomedicine applications. Adv. Funct. Mater. 2008, 18, 3745–3758.CrossRefGoogle Scholar
  10. [10]
    Benezra, M.; Penate-Medina, O.; Zanzonico, P. B.; Schaer, D.; Ow, H.; Burns, A.; DeStanchina, E.; Longo, V.; Herz, E.; Iyer, S. et al. Multimodal silica nanoparticles are effective cancertargeted probes in a model of human melanoma. J. Clin. Invest. 2011, 121, 2768–2780.CrossRefGoogle Scholar
  11. [11]
    Phillips, E.; Penate-Medina, O.; Zanzonico, P. B.; Carvajal, R. D.; Mohan, P.; Ye, Y. P.; Humm, J.; Gonen, M.; Kalaigian, H.; Schoder, H. et al. Clinical translation of an ultrasmall inorganic optical-pet imaging nanoparticle probe. Sci. Transl. Med. 2014, 6, 260ra149.CrossRefGoogle Scholar
  12. [12]
    Chen, F.; Ma, K.; Benezra, M.; Zhang, L.; Cheal, S. M.; Phillips, E.; Yoo, B.; Pauliah, M.; Overholtzer, M.; Zanzonico, P. et al. Cancer-targeting ultrasmall silica nanoparticles for clinical translation: Physicochemical structure and biological property correlations. Chem. Mater. 2017, 29, 8766–8779.CrossRefGoogle Scholar
  13. [13]
    Chen, F.; Ma, K.; Zhang, L.; Madajewski, B.; Zanzonico, P.; Sequeira, S.; Gonen, M.; Wiesner, U.; Bradbury, M. S. Target-or-clear zirconium-89 labeled silica nanoparticles for enhanced cancer-directed uptake in melanoma: A comparison of radiolabeling strategies. Chem. Mater. 2017, 29, 8269–8281.CrossRefGoogle Scholar
  14. [14]
    Chen, F.; Zhang, X. L.; Ma, K.; Madajewski, B.; Benezra, M.; Zhang, L.; Phillips, E.; Turker, M. Z.; Gallazzi, F.; Penate-Medina, O. et al. Melanocortin-1 receptor-targeting ultrasmall silica nanoparticles for dual-modality human melanoma imaging. ACSAppl. Mater. Interfaces 2018, 10, 4379–4393.CrossRefGoogle Scholar
  15. [15]
    Chen, F.; Goel, S.; Valdovinos, H. F.; Luo, H. M.; Hernandez, R.; Barnhart, T. E.; Cai, W. B. In vivo integrity and biological fate of chelator-free zirconium-89-labeled mesoporous silica nanoparticles. ACS Nano 2015, 9, 7950–7959.CrossRefGoogle Scholar
  16. [16]
    Shaffer, T. M.; Wall, M. A.; Harmsen, S.; Longo, V. A.; Drain, C. M.; Kircher, M. F.; Grimm, J. Silica nanoparticles as substrates for chelator-free labeling of oxophilic radioisotopes. Nano Lett. 2015, 15, 864–868.CrossRefGoogle Scholar
  17. [17]
    Shaffer, T. M.; Harmsen, S.; Khwaja, E.; Kircher, M. F.; Drain, C. M.; Grimm, J. Stable radiolabeling of sulfur-functionalized silica nanoparticles with copper-64. Nano Lett. 2016, 16, 5601–5604.CrossRefGoogle Scholar
  18. [18]
    Ellison, P. A.; Chen, F.; Goel, S.; Barnhart, T. E.; Nickles, R. J.; DeJesus, O. T.; Cai, W. B. Intrinsic and stable conjugation of thiolated mesoporous silica nanoparticles with radioarsenic. ACS Appl. Mater. Interfaces 2017, 9, 6772–6781.CrossRefGoogle Scholar
  19. [19]
    Chen, F.; Valdovinos, H. F.; Hernandez, R.; Goel, S.; Barnhart, T. E.; Cai, W. B. Intrinsic radiolabeling of titanium-45 using mesoporous silica nanoparticles. Acta Pharmacol. Sin. 2017, 38, 907–913.CrossRefGoogle Scholar
  20. [20]
    Lee, J. E.; Lee, N.; Kim, T.; Kim, J.; Hyeon, T. Multifunctional mesoporous silica nanocomposite nanoparticles for theranostic applications. Acc. Chem. Res. 2011, 44, 893–902.CrossRefGoogle Scholar
  21. [21]
    Tang, F. Q.; Li, L. L.; Chen, D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012, 24, 1504–1534.CrossRefGoogle Scholar
  22. [22]
    Chen, Y.; Chen, H. R.; Zeng, D. P.; Tian, Y. B.; Chen, F.; Feng, J. W.; Shi, J. L. Core/shell structured hollow mesoporous nanocapsules: A potential platform for simultaneous cell imaging and anticancer drug delivery. ACS Nano 2010, 4, 6001–6013.CrossRefGoogle Scholar
  23. [23]
    Chen, F.; Hong, H.; Zhang, Y.; Valdovinos, H. F.; Shi, S. X.; Kwon, G. S.; Theuer, C. P.; Barnhart, T. E.; Cai, W. B. In vivo tumor targeting and image-guided drug delivery with antibodyconjugated, radiolabeled mesoporous silica nanoparticles. ACS Nano 2013, 7, 9027–9039.CrossRefGoogle Scholar
  24. [24]
    Chen, F.; Hong, H.; Goel, S.; Graves, S. A.; Orbay, H.; Ehlerding, E. B.; Shi, S. X.; Theuer, C. P.; Nickles, R. J.; Cai, W. B. In vivo tumor vasculature targeting of CuS@MSN based theranostic nanomedicine. ACS Nano 2015, 9, 3926–3934.CrossRefGoogle Scholar
  25. [25]
    Chen, F.; Hong, H.; Shi, S. X.; Goel, S.; Valdovinos, H. F.; Hernandez, R.; Theuer, C. P.; Barnhart, T. E.; Cai, W. B. Engineering of hollow mesoporous silica nanoparticles for remarkably enhanced tumor active targeting efficacy. Sci. Rep. 2014, 4, 5080.CrossRefGoogle Scholar
  26. [26]
    Shi, S. X.; Chen, F.; Cai, W. B. Biomedical applications of functionalized hollow mesoporous silica nanoparticles: Focusing on molecular imaging. Nanomedicine 2013, 8, 2027–2039.CrossRefGoogle Scholar
  27. [27]
    Liu, J.; Qiao, S. Z.; Budi Hartono, S.; Lu, G. Q. Monodisperse yolk-shell nanoparticles with a hierarchical porous structure for delivery vehicles and nanoreactors. Angew. Chem., Int. Ed 2010, 49, 4981–4985.CrossRefGoogle Scholar
  28. [28]
    Chen, D.; Li, L. L.; Tang, F. Q.; Qi, S. Facile and scalable synthesis of tailored silica "nanorattle" structures. Adv. Mater. 2009, 21, 3804–3807.CrossRefGoogle Scholar
  29. [29]
    Fan, W. P.; Shen, B.; Bu, W. B.; Chen, F.; Zhao, K. L.; Zhang, S. J.; Zhou, L. P.; Peng, W. J.; Xiao, Q. F.; Xing, H. Y. et al. Rattle-structured multifunctional nanotheranostics for synergetic chemo-/radiotherapy and simultaneous magnetic/luminescent dual-mode imaging. J. Am. Chem. Soc. 2013, 135, 6494–6503.CrossRefGoogle Scholar
  30. [30]
    Liu, J. N.; Liu, Y.; Bu, W. B.; Bu, J. W.; Sun, Y.; Du, J. L.; Shi, J. L. Ultrasensitive nanosensors based on upconversion nanoparticles for selective hypoxia imaging in vivo upon near-infrared excitation. J. Am. Chem. Soc. 2014, 136, 9701–9709.CrossRefGoogle Scholar
  31. [31]
    Liu, Y. Y.; Liu, Y.; Bu, W. B.; Xiao, Q. F.; Sun, Y.; Zhao, K. L.; Fan, W. P.; Liu, J. N.; Shi, J. L. Radiation-/hypoxia-induced solid tumor metastasis and regrowth inhibited by hypoxiaspecific upconversion nanoradiosensitizer. Biomaterials 2015, 49, 1–8.CrossRefGoogle Scholar
  32. [32]
    Chen, Y.; Chen, H. R.; Guo, L. M.; He, Q. J.; Chen, F.; Zhou, J.; Feng, J. W.; Shi, J. L. Hollow/rattle-type mesoporous nanostructures by a structural difference-based selective etching strategy. ACS Nano 2010, 4, 529–539.CrossRefGoogle Scholar
  33. [33]
    Zhang, Q.; Zhang, T. R.; Ge, J. P.; Yin, Y. D. Permeable silica shell through surface-protected etching. Nano Lett. 2008, 8, 2867–2871.CrossRefGoogle Scholar
  34. [34]
    Lin, L. S.; Song, J. B.; Yang, H. H.; Chen, X. Y. Yolk-shell nanostructures: Design, synthesis, and biomedical applications. Adv. Mater. 2018, 30, 1704639.CrossRefGoogle Scholar
  35. [35]
    Liu, J.; Qiao, S. Z.; Chen, J. S.; Lou, X. W.; Xing, X. R.; Lu, G. Q. Yolk/shell nanoparticles: New platforms for nanoreactors, drug delivery and lithium-ion batteries. Chem. Commun. 2011, 47, 12578–12591.CrossRefGoogle Scholar
  36. [36]
    Priebe, M.; Fromm, K. M. Nanorattles or yolk-shell nanoparticles—what are they, how are they made, and what are they good for? Chem.—Eur. J. 2015, 21, 3854–3874.CrossRefGoogle Scholar
  37. [37]
    Fang, J.; Nakamura, H.; Maeda, H. The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv. Drug Deliv. Rev. 2011, 63, 136–151.CrossRefGoogle Scholar
  38. [38]
    Chen, F.; Cai, W. B. Tumor vasculature targeting: A generally applicable approach for functionalized nanomaterials. Small 2014, 10, 1887–1893.CrossRefGoogle Scholar
  39. [39]
    Seon, B. K.; Haba, A.; Matsuno, F.; Takahashi, N.; Tsujie, M.; She, X. W.; Harada, N.; Uneda, S.; Tsujie, T.; Toi, H. et al. Endoglin-targeted cancer therapy. Curr. Drug Deliv. 2011, 8, 135–143.CrossRefGoogle Scholar
  40. [40]
    Rosen, L. S.; Hurwitz, H. I.; Wong, M. K.; Goldman, J.; Mendelson, D. S.; Figg, W. D.; Spencer, S.; Adams, B. J.; Alvarez, D.; Seon, B. K. et al. A phase I first-in-human study of TRC105 (anti-endoglin antibody) in patients with advanced cancer. Clin. Cancer Res. 2012, 18, 4820–4829.CrossRefGoogle Scholar
  41. [41]
    Hong, H.; Yang, K.; Zhang, Y.; Engle, J. W.; Feng, L. Z.; Yang, Y.; Nayak, T. R.; Goel, S.; Bean, J.; Theuer, C. P. et al. In vivo targeting and imaging of tumor vasculature with radiolabeled, antibody-conjugated nanographene. ACS Nano 2012, 6, 2361–2370.CrossRefGoogle Scholar
  42. [42]
    Chen, F.; Nayak, T. R.; Goel, S.; Valdovinos, H. F.; Hong, H.; Theuer, C. P.; Barnhart, T. E.; Cai, W. B. In vivo tumor vasculature targeted PET/NIRF imaging with TRC105(fab)-conjugated, dual-labeled mesoporous silica nanoparticles. Mol. Pharmaceutics 2014, 11, 4007–4014.CrossRefGoogle Scholar
  43. [43]
    Goel, S.; Chen, F.; Luan, S. J.; Valdovinos, H. F.; Shi, S. X.; Graves, S. A.; Ai, F. R.; Barnhart, T. E.; Theuer, C. P.; Cai, W. B. Engineering intrinsically zirconium-89 radiolabeled self-destructing mesoporous silica nanostructures for in vivo biodistribution and tumor targeting studies. Adv. Sci. 2016, 3, 1600122.CrossRefGoogle Scholar
  44. [44]
    Zhou, J.; Liu, Z.; Li, F. Y. Upconversion nanophosphors for small-animal imaging. Chem. Soc. Rev. 2012, 41, 1323–1349.CrossRefGoogle Scholar
  45. [45]
    Haase, M.; Schäfer, H. Upconverting nanoparticles. Angew. Chem., Int. Ed. 2011, 50, 5808–5829.CrossRefGoogle Scholar
  46. [46]
    Ju, Q.; Tu, D. T.; Liu, Y. S.; Li, R. F.; Zhu, H. M.; Chen, J. C.; Chen, Z.; Huang, M. D.; Chen, X. Y. Amine-functionalized lanthanide-doped KGdF4 nanocrystals as potential optical/magnetic multimodal bioprobes. J. Am. Chem. Soc. 2012, 134, 1323–1330.CrossRefGoogle Scholar
  47. [47]
    Wu, S. W.; Han, G.; Milliron, D. J.; Aloni, S.; Altoe, V.; Talapin, D. V.; Cohen, B. E.; Schuck, P. J. Non-blinking and photostable upconverted luminescence from single lanthanide-doped nanocrystals. Proc. Natl. Acad. Sci. USA 2009, 106, 10917–10921.CrossRefGoogle Scholar
  48. [48]
    Cheng, L.; Wang, C.; Liu, Z. Upconversion nanoparticles and their composite nanostructures for biomedical imaging and cancer therapy. Nanoscale 2013, 5, 23–37.CrossRefGoogle Scholar
  49. [49]
    Park, Y. I.; Kim, J. H.; Lee, K. T.; Jeon, K. S.; Bin Na, H.; Yu, J. H.; Kim, H. M.; Lee, N.; Choi, S. H.; Baik, S. I. et al. Nonblinking and nonbleaching upconverting nanoparticles as an optical imaging nanoprobe and T1 magnetic resonance imaging contrast agent. Adv. Mater. 2009, 21, 4467–4471.CrossRefGoogle Scholar
  50. [50]
    Chatterjee, D. K.; Rufaihah, A. J.; Zhang, Y. Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals. Biomaterials 2008, 29, 937–943.CrossRefGoogle Scholar
  51. [51]
    Nam, S. H.; Bae, Y. M.; Park, Y. I.; Kim, J. H.; Kim, H. M.; Choi, J. S.; Lee, K. T.; Hyeon, T.; Suh, Y. D. Long-term real-time tracking of lanthanide ion doped upconverting nanoparticles in living cells. Angew. Chem., Int. Ed 2011, 50, 6093–6097.CrossRefGoogle Scholar
  52. [52]
    Xiong, L. Q.; Chen, Z. G.; Tian, Q. W.; Cao, T. Y.; Xu, C. J.; Li, F. Y High contrast upconversion luminescence targeted imaging in vivo using peptide-labeled nanophosphors. Anal. Chem. 2009, 81, 8687–8694.CrossRefGoogle Scholar
  53. [53]
    Chen, F.; Bu, W. B.; Zhang, S. J.; Liu, J. N.; Fan, W. P.; Zhou, L. P.; Peng, W. J.; Shi, J. L. Gd3+-ion-doped upconversion nanoprobes: Relaxivity mechanism probing and sensitivity optimization. Adv. Funct. Mater. 2013, 23, 298–307.CrossRefGoogle Scholar
  54. [54]
    Chen, F.; Bu, W. B.; Zhang, S. J.; Liu, X. H.; Liu, J. N.; Xing, H. Y.; Xiao, Q. F.; Zhou, L. P.; Peng, W. J.; Wang, L. Z. et al. Positive and negative lattice shielding effects co-existing in Gd (III) ion doped bifunctional upconversion nanoprobes. Adv. Funct. Mater. 2011, 21, 4285–4294.CrossRefGoogle Scholar
  55. [55]
    Chen, F.; Bu, W. B.; Chen, Y.; Fan, Y. C.; He, Q. J.; Zhu, M.; Liu, X. H.; Zhou, L. P.; Zhang, S. J.; Peng, W. J. et al. A sub-50-nm monosized superparamagnetic Fe3O4@SiO2 T2-weighted MRI contrast agent: Highly reproducible synthesis of uniform single-loaded core-shell nanostructures. Chem. — Asian J 2009, 4, 1809–1816.CrossRefGoogle Scholar
  56. [56]
    Taylor, K. M. L.; Kim, J. S.; Rieter, W. J.; An, H. Y.; Lin, W. L.; Lin, W. B. Mesoporous silica nanospheres as highly efficient MRI contrast agents. J. Am. Chem. Soc. 2008, 130, 2154–2155.CrossRefGoogle Scholar
  57. [57]
    Fang, X. L.; Chen, C.; Liu, Z. H.; Liu, P. X.; Zheng, N. F. A cationic surfactant assisted selective etching strategy to hollow mesoporous silica spheres. Nanoscale 2011, 3, 1632–1639.CrossRefGoogle Scholar
  58. [58]
    Chen, F.; Ellison, P. A.; Lewis, C. M.; Hong, H.; Zhang, Y.; Shi, S. X.; Hernandez, R.; Meyerand, M. E.; Barnhart, T. E.; Cai, W. B. Chelator-free synthesis of a dual-modality PET/MRI agent. Angew. Chem, Int. Ed 2013, 52, 13319–13323.CrossRefGoogle Scholar
  59. [59]
    Zhuravlev, L. T. The surface chemistry of amorphous silica. Zhuravlev model. Colloids Surf. A 2000, 173, 1–38.CrossRefGoogle Scholar
  60. [60]
    Fonsatti, E.; Nicolay, H. J.; Altomonte, M.; Covre, A.; Maio, M. Targeting cancer vasculature via endoglin/CD105: A novel antibody-based diagnostic and therapeutic strategy in solid tumours. Cardiovasc. Res. 2010, 86, 12–19. 15CrossRefGoogle Scholar
  61. [61]
    Tian, B.; Wang, Q. H.; Su, Q. Q.; Feng, W.; Li, F. Y. In vivo biodistribution and toxicity assessment of triplet-triplet annihilation-based upconversion nanocapsules. Biomaterials 2017, 112, 10–19.CrossRefGoogle Scholar
  62. [62]
    Sun, Y.; Feng, W.; Yang, P. Y.; Huang, C. H.; Li, F. Y. The biosafety of lanthanide upconversion nanomaterials. Chem. Soc. Rev. 2015, 44, 1509–1525.CrossRefGoogle Scholar
  63. [63]
    Feng, Q. Y.; Liu, Y. P.; Huang, J.; Chen, K.; Huang, J. X.; Xiao, K. Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Sci. Rep. 2018, 8, 2082.CrossRefGoogle Scholar
  64. [64]
    Singh, N.; Jenkins, G. J. S.; Asadi, R.; Doak, S. H. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev. 2010, 1, 5358.CrossRefGoogle Scholar
  65. [65]
    Tsoi, K. M.; Dai, Q.; Alman, B. A.; Chan, W. C. W. Are quantum dots toxic? Exploring the discrepancy between cell culture and animal studies. Acc. Chem. Res. 2013, 46, 662–671.Google Scholar
  66. [66]
    Ye, L.; Yong, K. T.; Liu, L. W.; Roy, I.; Hu, R.; Zhu, J.; Cai, H. X.; Law, W. C.; Liu, J. W.; Wang, K. et al. A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. Nat. Nanotechnol. 2012, 7, 453–458.CrossRefGoogle Scholar
  67. [67]
    Zhang, Y.; Hong, H.; Severin, G. W.; Engle, J. W.; Yang, Y.; Goel, S.; Nathanson, A. J.; Liu, G.; Nickles, R. J.; Leigh, B. R. et al. ImmunoPET and near-infrared fluorescence imaging of CD105 expression using a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. Am. J. Transl. Res. 2012, 4, 333–346.Google Scholar
  68. [68]
    Zhang, Y.; Hong, H.; Orbay, H.; Valdovinos, H. F.; Nayak, T. R.; Theuer, C. P.; Barnhart, T. E.; Cai, W. B. PET imaging of CD105/endoglin expression with a 61/64Cu-labeled Fab antibody fragment. Eur. J. Nucl. Med. Mol. Imaging 2013, 40, 759–767.CrossRefGoogle Scholar
  69. [69]
    Zhang, Y.; Hong, H.; Engle, J. W.; Yang, Y.; Barnhart, T. E.; Cai, W. Positron emission tomography and near-infrared fluorescence imaging of vascular endothelial growth factor with dual-labeled bevacizumab. Am. J. Nucl. Med. Mol. Imaging 2012, 2, 1–13.Google Scholar
  70. [70]
    Shi, S. X.; Yang, K.; Hong, H.; Valdovinos, H. F.; Nayak, T. R.; Zhang, Y.; Theuer, C. P.; Barnhart, T. E.; Liu, Z.; Cai, W. B. Tumor vasculature targeting and imaging in living mice with reduced graphene oxide. Biomaterials 2013, 34, 3002–3009.CrossRefGoogle Scholar
  71. [71]
    Hong, H.; Zhang, Y.; Severin, G. W.; Yang, Y.; Engle, J. W.; Niu, G.; Nickles, R. J.; Chen, X. Y.; Leigh, B. R.; Barnhart, T. E. et al. Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. Mol. Pharmaceutics 2012, 9, 2339–2349.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of RadiologyUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Materials Science ProgramUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Department of Medical PhysicsUniversity of Wisconsin-MadisonMadisonUSA
  4. 4.Department of Nuclear Medicine, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  5. 5.University of Wisconsin Carbone Cancer CenterMadisonUSA

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