Nano Research

, Volume 8, Issue 5, pp 1637–1647 | Cite as

Real-time in vivo visualization of tumor therapy by a near-infrared-II Ag2S quantum dot-based theranostic nanoplatform

  • Feng Hu
  • Chunyan Li
  • Yejun Zhang
  • Mao Wang
  • Dongming Wu
  • Qiangbin Wang
Research Article

Abstract

Real-time and objective feedback of therapeutic efficacies would be of great value for tumor treatment. Here, we report a smart Ag2S QD-based theranostic nanoplatform (DOX@PEG-Ag2S) obtained by loading the anti-cancer drug doxorubicin (DOX) into polyethylene glycol-coated silver sulfide quantum dots (PEG-Ag2S QDs) through hydrophobic-hydrophobic interactions, which exhibited high drug loading capability (93 wt.% of DOX to Ag2S QDs), long circulation in blood (t1/2 = 10.3 h), and high passive tumor-targeting efficiency (8.9% ID/gram) in living mice where % ID/gram reflects the probe concentration in terms of the percentage of the injected dose (ID) per gram of tissue. After targeting the tumor tissue, DOX from PEG-Ag2S cargoes was selectively and rapidly released into cancer cells, giving rise to a significant tumor inhibition. Owing to the deep tissue penetration and high spatio-temporal resolution of Ag2S QDs fluorescence in the second near-infrared window (NIR-II), the DOX@PEG-Ag2S enabled real-time in vivo reading of the drug targeting process and therapeutic efficacy. We expect that such a novel theranostic nanoplatform, DOX@PEG-Ag2S, with integrated drug delivery, therapy and assessment functionalities, will be highly useful for personalized treatments of tumors.

Keywords

in vivo imaging Ag2S quantum dots second near-infrared window fluorescence drug delivery tumor therapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

12274_2014_653_MOESM1_ESM.pdf (1.8 mb)
Supplementary material, approximately 1.81 MB.

Supplementary material, approximately 1.38 MB.

References

  1. [1]
    Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2013. CA: Cancer J. Clin. 2013, 63, 11–30.Google Scholar
  2. [2]
    Gregoriadis, G. Engineering liposomes for drug delivery: Progress and problems. Trends Biotechnol. 1995, 13, 527–537.CrossRefGoogle Scholar
  3. [3]
    O’Brien, M. E. R.; Wigler, N.; Inbar, M.; Rosso, R.; Grischke, E.; Santoro, A.; Catane, R.; Kieback, D. G.; Tomczak, P.; Ackland, S. P.; et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYXTM/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann. Oncol. 2004, 15, 440–449.CrossRefGoogle Scholar
  4. [4]
    Duncan, R. The dawning era of polymer therapeutics. Nat. Rev. Drug Discov. 2003, 2, 347–360.CrossRefGoogle Scholar
  5. [5]
    Duncan, R. Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer 2006, 6, 688–701.CrossRefGoogle Scholar
  6. [6]
    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
  7. [7]
    Shen, D. K.; Yang, J. P.; Li, X. M.; Zhou, L.; Zhang, R. Y.; Li, W.; Chen, L.; Wang, R.; Zhang, F.; Zhao, D. Y. Biphase stratification approach to three-dimensional dendritic biodegradable mesoporous silica nanospheres. Nano Lett. 2014, 14, 923–932.CrossRefGoogle Scholar
  8. [8]
    Terentyuk, G.; Panfilova, E.; Khanadeev, V.; Chumakov, D.; Genina, E.; Bashkatov, A.; Tuchin, V.; Bucharskaya, A.; Maslyakova, G.; Khlebtsov, N.; et al. Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo. Nano Res. 2014, 7, 325–337.CrossRefGoogle Scholar
  9. [9]
    Yoo, D.; Lee, J.-H.; Shin, T.-H.; Cheon, J. Theranostic magnetic nanoparticles. Acc. Chem. Res. 2011, 44, 863–874.CrossRefGoogle Scholar
  10. [10]
    Ling, D.; Park, W.; Park, S.-J.; Lu, Y.; Kim, K. S.; Hackett, M. J.; Kim, B. H.; Yim, H.; Jeon, Y. S.; Na, K.; et al. Multifunctional tumor pH-sensitive self-assembled nanoparticles for bimodal imaging and treatment of resistant heterogeneous tumors. J. Am. Chem. Soc. 2014, 136, 5647–5655.CrossRefGoogle Scholar
  11. [11]
    Xing, R. J.; Bhirde, A. A.; Wang, S. J.; Sun, X. L.; Liu, G.; Hou, Y. L.; Chen, X. Y. Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles. Nano Res. 2013, 6, 1–9.CrossRefGoogle Scholar
  12. [12]
    Qian, X. M.; Peng, X. H.; Ansari, D. O.; Yin-Goen, Q.; Chen, G. Z.; Shin, D. M.; Yang, L.; Young, A. N.; Wang, M. D.; Nie, S. M. In vivo tumor targeting and spectroscopic detection with surface-enhanced raman nanoparticle tags. Nat. Biotechnol. 2008, 26, 83–90.CrossRefGoogle Scholar
  13. [13]
    Rosi, N. L.; Mirkin, C. A. Nanostructures in biodiagnostics. Chem. Rev. 2005, 105, 1547–1562.CrossRefGoogle Scholar
  14. [14]
    Hu, M.; Chen, J. Y.; Li, Z.-Y.; Au, L.; Hartland, G. V.; Li, X. D.; Marquez, M.; Xia, Y. N. Gold nanostructures: engineering their plasmonic properties for biomedical applications. Chem. Soc. Rev. 2006, 35, 1084–1094.CrossRefGoogle Scholar
  15. [15]
    Dreaden, E. C.; Mackey, M. A.; Huang, X. H.; Kang, B.; El-Sayed, M. A. Beating cancer in multiple ways using nanogold. Chem. Soc. Rev. 2011, 40, 3391–3404.CrossRefGoogle Scholar
  16. [16]
    Zhang, B.; Price, J.; Hong, G. S.; Tabakman, S. M.; Wang, H. L.; Jarrell, J. A.; Feng, J.; Utz, P. J.; Dai, H. J. Multiplexed cytokine detection on plasmonic gold substrates with enhanced near-infrared fluorescence. Nano Res. 2013, 6, 113–120.CrossRefGoogle Scholar
  17. [17]
    Liu, Y.; Yin, J.-J.; Nie, Z. H. Harnessing the collective properties of nanoparticle ensembles for cancer theranostics. Nano Res. 2014, 7, 1719–1730.CrossRefGoogle Scholar
  18. [18]
    Cheng, L.; Wang, C.; Feng, L. Z.; Yang, K.; Liu, Z. Functional nanomaterials for phototherapies of cancer. Chem. Rev. 2014, 114, 10869–10939.CrossRefGoogle Scholar
  19. [19]
    Allen, T. M.; Cullis, P. R. Drug delivery systems: Entering the mainstream. Science 2004, 303, 1818–1822.CrossRefGoogle Scholar
  20. [20]
    Bakueva, L.; Gorelikov, I.; Musikhin, S.; Zhao, X. S.; Sargent, E. H.; Kumacheva, E. PbS quantum dots with stable efficient luminescence in the near-IR spectral range. Adv. Mater. 2004, 16, 926–929.CrossRefGoogle Scholar
  21. [21]
    Wehrenberg, B. L.; Wang, C. J.; Guyot-Sionnest, P. Interband and intraband optical studies of PbSe colloidal quantum dots. J. Phys. Chem. B 2002, 106, 10634–10640.CrossRefGoogle Scholar
  22. [22]
    Dong, B. H.; Li, C. Y.; Chen, G. C.; Zhang, Y. J.; Zhang, Y.; Deng, M. J.; Wang, Q. B. Facile synthesis of highly photoluminescent Ag2Se quantum dots as a new fluorescent probe in the second near-infrared window for in vivo imaging. Chem. Mater. 2013, 25, 2503–2509.CrossRefGoogle Scholar
  23. [23]
    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 near-infrared imaging in mice. Nat. Nanotechnol. 2009, 4, 773–780.CrossRefGoogle Scholar
  24. [24]
    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. Through-skull fluorescence imaging of the brain in a new near-infrared window. Nat. Photonics 2014, 8, 723–730.CrossRefGoogle Scholar
  25. [25]
    Du, Y. P.; Xu, B.; Fu, T.; Cai, M.; Li, F.; Zhang, Y.; Wang, Q. B. Near-infrared photoluminescent Ag2S quantum dots from a single source precursor. J. Am. Chem. Soc. 2010, 132, 1470–1471.CrossRefGoogle Scholar
  26. [26]
    Zhang, Y.; Hong, G. S.; Zhang, Y. J.; Chen, G. C.; Li, F.; Dai, H. J.; Wang, Q. B. Ag2S quantum dot: A bright and biocompatible fluorescent nanoprobe in the second near-infrared window. ACS Nano 2012, 6, 3695–3702.CrossRefGoogle Scholar
  27. [27]
    Hong, G. S.; Robinson, J. T.; Zhang, Y. J.; Diao, S.; Antaris, A. L.; Wang, Q. B.; Dai, H. J. In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. Angew. Chem. Int. Ed. 2012, 51, 9818–9821.CrossRefGoogle Scholar
  28. [28]
    Chen, G. C.; Tian, F.; Zhang, Y.; Zhang, Y. J.; Li, C. Y.; Wang, Q. B. Tracking of transplanted human mesenchymal stem cells in living mice using near-infrared Ag2S quantum dots. Adv. Funct. Mater. 2014, 24, 2481–2488.CrossRefGoogle Scholar
  29. [29]
    Li, C. Y.; Zhang, Y. J.; Wang, M.; Zhang, Y.; Chen, G. C.; Li, L.; Wu, D. M.; Wang, Q. B. In vivo real-time visualization of tissue blood flow and angiogenesis using Ag2S quantum dots in the NIR-II window. Biomaterials 2014, 35, 393–400.CrossRefGoogle Scholar
  30. [30]
    Zhang, Y. J.; Liu, Y. S.; Li, C. Y.; Chen, X. Y.; Wang, Q. B. Controlled synthesis of Ag2S quantum dots and experimental determination of the exciton Bohr radius. J. Phys. Chem. C 2014, 118, 4918–4923.CrossRefGoogle Scholar
  31. [31]
    Prencipe, G.; Tabakman, S. M.; Welsher, K.; Liu, Z.; Goodwin, A. P.; Zhang, L.; Henry, J.; Dai, H. J. PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. J. Am. Chem. Soc. 2009, 131, 4783–4787.CrossRefGoogle Scholar
  32. [32]
    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.CrossRefGoogle Scholar
  33. [33]
    Yao, L. M.; Zhou, J.; Liu, J. L.; Feng, W.; Li, F. Y. Iridium-complex-modified upconversion nanophosphors for effective LRET detection of cyanide anions in pure water. Adv. Funct. Mater. 2012, 22, 2667–2672.CrossRefGoogle Scholar
  34. [34]
    Gao, Y.; Chen, Y.; Ji, X. F.; He, X. Y.; Yin, Q.; Zhang, Z. W.; Shi, J. L.; Li, Y. P. Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles. ACS Nano 2011, 5, 9788–9798.CrossRefGoogle Scholar
  35. [35]
    Ballou, B.; Lagerholm, B. C.; Ernst, L. A.; Bruchez, M. P.; Waggoner, A. S. Noninvasive Imaging of Quantum Dots in Mice. Bioconjugate Chem. 2004, 15, 79–86.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Feng Hu
    • 1
  • Chunyan Li
    • 1
  • Yejun Zhang
    • 1
  • Mao Wang
    • 1
  • Dongming Wu
    • 1
  • Qiangbin Wang
    • 1
  1. 1.Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine and i-Lab, Suzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhouChina

Personalised recommendations