Advertisement

Nano Research

, Volume 12, Issue 2, pp 273–279 | Cite as

A theranostic agent for cancer therapy and imaging in the second near-infrared window

  • Zhuoran Ma
  • Hao Wan
  • Weizhi Wang
  • Xiaodong Zhang
  • Takaaki Uno
  • Qianglai Yang
  • Jingying Yue
  • Hongpeng Gao
  • Yeteng Zhong
  • Ye Tian
  • Qinchao Sun
  • Yongye Liang
  • Hongjie DaiEmail author
Research Article
  • 169 Downloads

Abstract

Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000–1,700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanoparticles to afford specific binding to molecular folate receptors on murine breast cancer 4T1 tumor cells. In vivo, the nanoparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0 ± 2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-II theranostic agent developed.

Keywords

theranostic nanoparticles second near-infrared window fluorescence imaging cancer therapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgements

This study was supported by National Institutes of Health NIH DP1-NS-105737, the Deng family gift, and the Shenzhen Peacock Program Grant KQTD20140630160825828.

Supplementary material

12274_2018_2210_MOESM1_ESM.pdf (2 mb)
A theranostic agent for cancer therapy and imaging in the second near-infrared window

References

  1. [1]
    Janib, S. M.; Moses, A. S.; MacKay, J. A. Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Deliv. Rev. 2010, 62, 1052–1063.CrossRefGoogle Scholar
  2. [2]
    Wicki, A.; Witzigmann, D.; Balasubramanian, V.; Huwyler, J. Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications. J. Control. Release 2015, 200, 138–157.CrossRefGoogle Scholar
  3. [3]
    Maeda, H.; Nakamura, H.; Fang, J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv. Drug Deliv. Rev. 2013, 65, 71–79.CrossRefGoogle Scholar
  4. [4]
    Cole, A. J.; Yang, V. C.; David, A. E. Cancer theranostics: The rise of targeted magnetic nanoparticles. Trends Biotechnol. 2011, 29, 323–332.CrossRefGoogle Scholar
  5. [5]
    Lee, G. Y.; Qian, W. P.; Wang, L. Y.; Wang, Y. A.; Staley, C. A.; Satpathy, M.; Nie, S. M.; Mao, H.; Yang, L. Theranostic nanoparticles with controlled release of gemcitabine for targeted therapy and MRI of pancreatic cancer. ACS Nano 2013, 7, 2078–2089.CrossRefGoogle Scholar
  6. [6]
    Liu, T.; Wu, G. Y.; Cheng, J. J.; Lu, Q.; Yao, Y. J.; Liu, Z. J.; Zhu, D. C.; Zhou, J.; Xu, J. R.; Zhu, J. et al. Multifunctional lymph-targeted platform based on Mn@mSiO2 nanocomposites: Combining PFOB for dual-mode imaging and DOX for cancer diagnose and treatment. Nano Res. 2016, 9, 473–489.CrossRefGoogle Scholar
  7. [7]
    Zhou, M.; Song, S. L.; Zhao, J.; Tian, M.; Li, C. Theranostic CuS nanoparticles targeting folate receptors for PET image-guided photothermal therapy. J. Mater. Chem. B 2015, 3, 8939–8948.CrossRefGoogle Scholar
  8. [8]
    Baum, R. P.; Kulkarni, H. R. THERANOSTICS: From molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy—The Bad Berka experience. Theranostics 2012, 2, 437–447.CrossRefGoogle Scholar
  9. [9]
    Nurunnabi, M.; Cho, K. J.; Choi, J. S.; Huh, K. M.; Lee, Y. K. Targeted near-IR QDs-loaded micelles for cancer therapy and imaging. Biomaterials 2010, 31, 5436–5444.CrossRefGoogle Scholar
  10. [10]
    Ge, J. C.; Jia, Q. Y.; Liu, W. M.; Guo, L.; Liu, Q. Y.; Lan, M. H.; Zhang, H. Y.; Meng, X. M.; Wang, P. F. Red-emissive carbon dots for fluorescent, photoacoustic, and thermal theranostics in living mice. Adv. Mater. 2015, 27, 4169–4177.CrossRefGoogle Scholar
  11. [11]
    Wu, X. M.; Sun, X. R.; Guo, Z. Q.; Tang, J. B.; Shen, Y. Q.; James, T. D.; Tian, H.; Zhu, W. H. In vivo and in situ tracking cancer chemotherapy by highly photostable NIR fluorescent theranostic prodrug. J. Am. Chem. Soc. 2014, 136, 3579–3588.CrossRefGoogle Scholar
  12. [12]
    Smith, B. R.; Gambhir, S. S. Nanomaterials for in vivo imaging. Chem. Rev. 2017, 117, 901–986.CrossRefGoogle Scholar
  13. [13]
    Stolik, S.; Delgado, J. A.; Pérez, A.; Anasagasti, L. Measurement of the penetration depths of red and near infrared light in human “ex vivo” tissues. J. Photochem. Photobiol. B 2000, 57, 90–93.CrossRefGoogle Scholar
  14. [14]
    Frangioni, J. V. In vivo near-infrared fluorescence imaging. Curr. Opin. Chem. Biol. 2003, 7, 626–634.CrossRefGoogle Scholar
  15. [15]
    Tagaya, N.; Yamazaki, R.; Nakagawa, A.; Abe, A.; Hamada, K.; Kubota, K.; Oyama, T. Intraoperative identification of sentinel lymph nodes by nearinfrared fluorescence imaging in patients with breast cancer. Am. J. Surg. 2008, 195, 850–853.CrossRefGoogle Scholar
  16. [16]
    He, X. X.; Wu, X.; Wang, K. M.; Shi, B. H.; Hai, L. Methylene blueencapsulated phosphonate-terminated silica nanoparticles for simultaneous in vivo imaging and photodynamic therapy. Biomaterials 2009, 30, 5601–5609.CrossRefGoogle Scholar
  17. [17]
    Smith, A. M.; Mancini, M. C.; Nie, S. M. Bioimaging: Second window for in vivo imaging. Nat. Nanotechnol. 2009, 4, 710–711.CrossRefGoogle Scholar
  18. [18]
    Hong, G. S.; Diao, S.; Chang, J. L.; Antaris, A. L.; Chen, C. X.; Zhang, B.; Zhao, S.; Atochin, D. N.; Huang, P. L.; Andreasson, K. I. et al. Throughskull fluorescence imaging of the brain in a new near-infrared window. Nat. Photonics 2014, 8, 723–730.CrossRefGoogle Scholar
  19. [19]
    Diao, S.; Blackburn, J. L.; Hong, G. S.; Antaris, A. L.; Chang, J. L.; Wu, J. Z.; Zhang, B.; Cheng, K.; Kuo, C. J.; Dai, H. J. Fluorescence imaging in vivo at wavelengths beyond 1500 nm. Angew. Chem. 2015, 127, 14971–14975.CrossRefGoogle Scholar
  20. [20]
    Zebibula, A.; Alifu, N.; Xia, L. Q.; Sun, C. W.; Yu, X. M.; Xue, D. W.; Liu, L. W.; Li, G. H.; Qian, J. Ultrastable and biocompatible NIRII quantum dots for functional bioimaging. Adv. Funct. Mater. 2018, 28, 1703451.CrossRefGoogle Scholar
  21. [21]
    Naczynski, D. J.; Tan, M. C.; Zevon, M.; Wall, B.; Kohl, J.; Kulesa, A.; Chen, S.; Roth, C. M.; Riman, R. E.; Moghe, P. V. Rare-earth-doped biological composites as in vivo shortwave infrared reporters. Nat. Commun. 2013, 4, 2199.CrossRefGoogle Scholar
  22. [22]
    Singla, A. K.; Garg, A.; Aggarwal, D. Paclitaxel and its formulations. Int. J. Pharm. 2002, 235, 179–192.CrossRefGoogle Scholar
  23. [23]
    Kim, S. C.; Kim, D. W.; Shim, Y. H.; Bang, J. S.; Oh, H. S.; Kim, S. W.; Seo, M. H. In vivo evaluation of polymeric micellar paclitaxel formulation: Toxicity and efficacy. J. Control. Release 2001, 72, 191–202.CrossRefGoogle Scholar
  24. [24]
    Yang, Q. L.; Ma, Z. R.; Wang, H. S.; Zhou, B.; Zhu, S. J.; Zhong, Y. T.; Wang, J. Y.; Wan, H.; Antaris, A.; Ma, R. et al. Rational design of molecular fluorophores for biological imaging in the NIR-II window. Adv. Mater. 2017, 29, 1605497.CrossRefGoogle Scholar
  25. [25]
    Wan, H.; Yue, J. Y.; Zhu, S. J.; Uno, T.; Zhang, X. D.; Yang, Q. L.; Yu, K.; Hong, G. S.; Wang, J. Y.; Li, L. L. et al. A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues. Nat. Commun. 2018, 9, 1171.CrossRefGoogle Scholar
  26. [26]
    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.CrossRefGoogle Scholar
  27. [27]
    Chen, L. X.; Zhang, Y. M.; Cao, Y.; Zhang, H. Y.; Liu, Y. Bridged bis(β-cyclodextrin)s-based polysaccharide nanoparticles for controlled paclitaxel delivery. RSC Adv. 2016, 6, 28593–28598.CrossRefGoogle Scholar
  28. [28]
    Song, Y. C.; Shi, W.; Chen, W.; Li, X. H.; Ma, H. M. Fluorescent carbon nanodots conjugated with folic acid for distinguishing folate-receptor-positive cancer cells from normal cells. J. Mater. Chem. 2012, 22, 12568–12573.CrossRefGoogle Scholar
  29. [29]
    Biabanikhankahdani, R.; Bayat, S.; Ho, K. L.; Alitheen, N. B. M.; Tan, W. S. A simple add-and-display method for immobilisation of cancer drug on his-tagged virus-like nanoparticles for controlled drug delivery. Sci. Rep. 2017, 7, 5303.CrossRefGoogle Scholar
  30. [30]
    Murphy, J. E.; Beard, M. C.; Norman, A. G.; Ahrenkiel, S. P.; Johnson, J. C.; Yu, P. R.; Mićić, O. I.; Ellingson, R. J.; Nozik, A. J. PbTe colloidal nanocrystals: Synthesis, characterization, and multiple exciton generation. J. Am. Chem. Soc. 2006, 128, 3241–3247.CrossRefGoogle Scholar
  31. [31]
    Sun, Y.; Qu, C. R.; Chen, H.; He, M. M.; Tang, C.; Shou, K. Q.; Hong, S.; Yang, M.; Jiang, Y. X.; Ding, B. B. et al. Novel benzo-bis(1,2,5-thiadiazole) fluorophores for in vivo NIR-II imaging of cancer. Chem. Sci. 2016, 7, 6203–6207.CrossRefGoogle Scholar
  32. [32]
    Semonin, O. E.; Johnson, J. C.; Luther, J. M.; Midgett, A. G.; Nozik, A. J.; Beard, M. C. Absolute photoluminescence quantum yields of IR-26 dye, PbS, and PbSe quantum dots. J. Phys. Chem. Lett. 2010, 1, 2445–2450.CrossRefGoogle Scholar
  33. [33]
    Hatami, S.; Würth, C.; Kaiser, M.; Leubner, S.; Gabriel, S.; Bahrig, L.; Lesnyak, V.; Pauli, J.; Gaponik, N.; Eychmüller, A. et al. Absolute photoluminescence quantum yields of IR26 and IR-emissive Cd1−x Hgx Te and PbS quantum dots—Method- and material-inherent challenges. Nanoscale 2015, 7, 133–143.CrossRefGoogle Scholar
  34. [34]
    Welsher, K.; Liu, Z.; Sherlock, S. P.; Robinson, J. T.; Chen, Z.; Daranciang, D.; Dai, H. J. A route to brightly fluorescent carbon nanotubes for nearinfrared imaging in mice. Nat. Nanotechnol. 2009, 4, 773–780.CrossRefGoogle Scholar
  35. [35]
    Hong, G. S.; Lee, J. C.; Robinson, J. T.; Raaz, U.; Xie, L. M.; Huang, N. F.; Cooke, J. P.; Dai, H. J. Multifunctional in vivo vascular imaging using near-infrared II fluorescence. Nat. Med. 2012, 18, 1841–1846.CrossRefGoogle Scholar
  36. [36]
    Alibolandi, M.; Abnous, K.; Sadeghi, F.; Hosseinkhani, H.; Ramezani, M.; Hadizadeh, F. Folate receptor-targeted multimodal polymersomes for delivery of quantum dots and doxorubicin to breast adenocarcinoma: In vitro and in vivo evaluation. Int. J. Pharm. 2016, 500, 162–178.CrossRefGoogle Scholar
  37. [37]
    Karimi Shervedani, R.; Yaghoobi, F.; Torabi, M.; Samiei Foroushani, M. Nanobioconjugated system formed of folic acid–deferrioxamine–Ga(III) on gold surface: Preparation, characterization, and activities for capturing of mouse breast cancer cells 4T1. J. Phys. Chem. C 2016, 120, 23212–23220.CrossRefGoogle Scholar
  38. [38]
    Gao, Z. G.; Tian, L.; Hu, J.; Park, I. S.; Bae, Y. H. Prevention of metastasis in a 4T1 murine breast cancer model by doxorubicin carried by folate conjugated pH sensitive polymeric micelles. J. Control. Release 2011, 152, 84–89.CrossRefGoogle Scholar
  39. [39]
    Liu, S. Q.; Wiradharma, N.; Gao, S. J.; Tong, Y. W.; Yang, Y. Y. Biofunctional micelles self-assembled from a folate-conjugated block copolymer for targeted intracellular delivery of anticancer drugs. Biomaterials 2007, 28, 1423–1433.CrossRefGoogle Scholar
  40. [40]
    Zhu, S. J.; Yang, Q. L.; Antaris, A. L.; Yue, J. Y.; Ma, Z. R.; Wang, H. S.; Huang, W.; Wan, H.; Wang, J.; Diao, S. et al. Molecular imaging of biological systems with a clickable dye in the broad 800- to 1,700-nm near-infrared window. Proc. Natl. Acad. Sci. USA 2017, 114, 962–967.CrossRefGoogle Scholar
  41. [41]
    Wang, W. Z.; Ma, Z. R.; Zhu, S. J.; Wan, H.; Yue, J. Y.; Ma, H. L.; Ma, R.; Yang, Q. L.; Wang, Z. H.; Li, Q. et al. Molecular cancer imaging in the second near-infrared window using a renal-excreted NIR-II fluorophorepeptide probe. Adv. Mater. 2018, 30, 1800106.CrossRefGoogle Scholar
  42. [42]
    O’Toole, S. A.; Sheppard, B. L.; McGuinness, E. P. J.; Gleeson, N. C.; Yoneda, M.; Bonnar, J. The MTS assay as an indicator of chemosensitivity/ resistance in malignant gynaecological tumours. Cancer Detect. Prev. 2003, 27, 47–54.CrossRefGoogle Scholar
  43. [43]
    Zubris, K. A. V.; Liu, R.; Colby, A.; Schulz, M. D.; Colson, Y. L.; Grinstaff, M. W. In vitro activity of paclitaxel-loaded polymeric expansile nanoparticles in breast cancer cells. Biomacromolecules 2013, 14, 2074–2082.CrossRefGoogle Scholar
  44. [44]
    Yi, X. L.; Lian, X. H.; Dong, J. X.; Wan, Z. Y.; Xia, C. Y.; Song, X.; Fu, Y.; Gong, T.; Zhang, Z. R. Co-delivery of pirarubicin and paclitaxel by human serum albumin nanoparticles to enhance antitumor effect and reduce systemic toxicity in breast cancers. Mol. Pharmaceutics 2015, 12, 4085–4098.CrossRefGoogle Scholar
  45. [45]
    Zhang, X. D.; Wang, H. S.; Antaris, A. L.; Li, L. L.; Diao, S.; Ma, R.; Nguyen, A.; Hong, G. S.; Ma, Z. R.; Wang, J. et al. Traumatic brain injury imaging in the second near-infrared window with a molecular fluorophore. Adv. Mater. 2016, 28, 6872–6879.CrossRefGoogle Scholar
  46. [46]
    Onda, N.; Kimura, M.; Yoshida, T.; Shibutani, M. Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging. Int. J. Cancer 2016, 139, 673–682.CrossRefGoogle Scholar
  47. [47]
    Hong, G. S.; Antaris, A. L.; Dai, H. J. Near-infrared fluorophores for biomedical imaging. Nat. Biomed. Eng. 2017, 1, 0010.CrossRefGoogle Scholar
  48. [48]
    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
  49. [49]
    Oh, N.; Park, J. H. Endocytosis and exocytosis of nanoparticles in mammalian cells. Int. J. Nanomedicine 2014, 9, 51–63.Google Scholar
  50. [50]
    Day, K. E.; Sweeny, L.; Kulbersh, B.; Zinn, K. R.; Rosenthal, E. L. Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma. Mol. Imaging Biol. 2013, 15, 722–729.CrossRefGoogle Scholar
  51. [51]
    Knutson, S.; Raja, E.; Bomgarden, R.; Nlend, M.; Chen, A.; Kalyanasundaram, R.; Desai, S. Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer. PLoS One 2016, 11, e0157762.CrossRefGoogle Scholar
  52. [52]
    Cheng, Z.; Wu, Y.; Xiong, Z. M.; Gambhir, S. S.; Chen, X. Y. Nearinfrared fluorescent RGD peptides for optical imaging of integrin αvβ3 expression in living mice. Bioconjug. Chem. 2005, 16, 1433–1441.CrossRefGoogle Scholar
  53. [53]
    Choi, H. S.; Gibbs, S. L.; Lee, J. H.; Kim, S. H.; Ashitate, Y.; Liu, F. B.; Hyun, H.; Park, G.; Xie, Y.; Bae, S. et al. Targeted zwitterionic nearinfrared fluorophores for improved optical imaging. Nat. Biotechnol. 2013, 31, 148–153.CrossRefGoogle Scholar
  54. [54]
    Peng, M. Y.; Qin, S. Y.; Jia, H. Z.; Zheng, D. W.; Rong, L.; Zhang, X. Z. Self-delivery of a peptide-based prodrug for tumor-targeting therapy. Nano Res. 2016, 9, 663–673.CrossRefGoogle Scholar
  55. [55]
    Wang, Z. G.; Fu, B. S.; Zou, S. W.; Duan, B.; Chang, C. Y.; Yang, B.; Zhou, X.; Zhang, L. Facile construction of carbon dots via acid catalytic hydrothermal method and their application for target imaging of cancer cells. Nano Res. 2016, 9, 214–223.CrossRefGoogle Scholar
  56. [56]
    Wang, D. L.; Liu, B.; Ma, Y.; Wu, C. W.; Mou, Q. B.; Deng, H. P.; Wang, R. B.; Yan, D. Y.; Zhang, C.; Zhu, X. Y. A molecular recognition approach to synthesize nucleoside analogue based multifunctional nanoparticles for targeted cancer therapy. J. Am. Chem. Soc. 2017, 139, 14021–14024.CrossRefGoogle Scholar
  57. [57]
    Gelderblom, H.; Verweij, J.; Nooter, K.; Sparreboom, A. Cremophor EL: The drawbacks and advantages of vehicle selection for drug formulation. Eur. J. Cancer 2001, 37, 1590–1598.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Zhuoran Ma
    • 1
  • Hao Wan
    • 1
  • Weizhi Wang
    • 2
  • Xiaodong Zhang
    • 3
  • Takaaki Uno
    • 4
  • Qianglai Yang
    • 5
  • Jingying Yue
    • 1
  • Hongpeng Gao
    • 1
  • Yeteng Zhong
    • 1
  • Ye Tian
    • 1
  • Qinchao Sun
    • 1
  • Yongye Liang
    • 5
  • Hongjie Dai
    • 1
    Email author
  1. 1.Department of ChemistryStanford UniversityStanfordUSA
  2. 2.CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijingChina
  3. 3.Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing TechnologySchool of SciencesTianjinChina
  4. 4.JSR Corporation Advanced Materials Research LaboratoriesYokkaichi, MieJapan
  5. 5.Department of Materials Science and EngineeringSouth University of Science and Technology of ChinaShenzhenChina

Personalised recommendations