, Volume 3, Issue 2, pp 208–215 | Cite as

Water-Soluble Upconversion Nanoparticles by Micellar Route

  • Sounderya NagarajanEmail author
  • Victor Roullier
  • Marian Amela Cortes
  • Muthu Kumara Gnanasamandham
  • Aurélien Dif
  • Fabien Grasset
  • Yong Zhang
  • Valerie MarchiEmail author


Upconversion nanoparticles (UCNs) have been of interest in applications such as biological imaging and sensing because of properties like low autofluorescence and negligible photobleaching. In this paper, a micellar encapsulation route was worked upon to make hydrophilic UCNs that are compatible with biological systems and enable conjugation of biomolecules. Phospholipid micelles cannot be easily synthesized with chemical recognition groups of biological interest so synthetic amphiphiles with suitable functional head groups were used to encapsulate and solubilize the hydrophobic UCNs. The encapsulated nanoparticles were characterized using transmission electron microscopy, fluorescence spectroscopy, and dynamic light scattering. The micelle-encapsulated UCNs had an average diameter of 125 nm and the fluorescence emission at 540/660 nm of the bare UCNs did not show any shift after encapsulation. The cytotoxicity of the micelle-encapsulated UCNs was tested using lactose dehydrogenase/MTS (tetrazole salt) assays. The cell viability was estimated to be 80 % at the working concentration of the micelle-encapsulated UCNs. Finally, the micelle-encapsulated UCNs bearing Arg-Gly-Asp tripeptidic RGD surface functionalization were tested on cancer cells expressing integrins for specificity. The micelle-encapsulated UCNs were found to be suitable for cellular targeting and imaging.


Upconversion Nanoparticles Micelle modification Imaging Cancer 



We would like to thank National University of Singapore AcRF grants for the funding of this work and also the Merlion Fellowship 2007 funded by French Embassy in making the collaboration possible.


  1. 1.
    Abdul Jalil, R., & Zhang, Y. (2008). Biocompatibility of silica coated NaYF4 upconversion fluorescent nanocrystals. Biomaterials, 29(30), 4122–4128.CrossRefGoogle Scholar
  2. 2.
    Diamente, P. R., Burke, R. D., van Veggel, F. C. J. M. (2005). Bioconjugation of Ln3+-doped LaF3 nanoparticles to avidin. Langmuir, 22(4), 1782–1788. doi: 10.1021/la052589r.CrossRefGoogle Scholar
  3. 3.
    Sivakumar, S., van Veggel, F. C. J. M., Raudsepp, M. (2005). Bright white light through up-conversion of a single NIR source from Sol−Gel-derived thin film made with Ln3+-doped LaF3 nanoparticles. Journal of the American Chemical Society, 127(36), 12464–12465. doi: 10.1021/ja052583o.CrossRefGoogle Scholar
  4. 4.
    Boyer, J.-C., Vetrone, F., Cuccia, L. A., Capobianco, J. A. (2006). Synthesis of colloidal upconverting NaYF4 nanocrystals doped with Er3+, Yb3+ and Tm3+, Yb3+ via thermal decomposition of lanthanide trifluoroacetate precursors. Journal of the American Chemical Society, 128(23), 7444–7445. doi: 10.1021/ja061848b.CrossRefGoogle Scholar
  5. 5.
    Hewes, R. A., & Sarver, J. F. (1969). Infrared excitation processes for the visible luminescence of Er3+, Ho3+, and Tm3+ in Yb3 +-sensitized rare-earth trifluorides. Physical Review, 182(2), 427.CrossRefGoogle Scholar
  6. 6.
    Wei, Y., Lu, F., Zhang, X., Chen, D. (2008). Polyol-mediated synthesis and luminescence of lanthanide-doped NaYF4 nanocrystal upconversion phosphors. Journal of Alloys and Compounds, 455(1–2), 376–384.CrossRefGoogle Scholar
  7. 7.
    Li, Z., Zhang, Y., Shuter, B., Muhammad Idris, N. (2009). Hybrid lanthanide nanoparticles with paramagnetic shell coated on upconversion fluorescent nanocrystals. Langmuir, 25(20), 12015–12018. doi: 10.1021/la903113u.CrossRefGoogle Scholar
  8. 8.
    Chatterjee, D. K., Rufaihah, A. J., Zhang, Y. (2008). Upconversion fluorescence imaging of cells and small animals using lanthanide doped nanocrystals. Biomaterials, 29(7), 937–943.CrossRefGoogle Scholar
  9. 9.
    Idris, N. M., Li, Z., Ye, L., Wei Sim, E. K., Mahendran, R., Ho, P. C.-L., et al. (2009). Tracking transplanted cells in live animal using upconversion fluorescent nanoparticles. Biomaterials, 30(28), 5104–5113.CrossRefGoogle Scholar
  10. 10.
    Wu, S., Han, G., Milliron, D. J., Aloni, S., Altoe, V., Talapin, D. V., et al. (2009). Non-blinking and photostable upconverted luminescence from single lanthanide-doped nanocrystals. Proceedings of the National Academy of Sciences, 106(27), 10917–10921. doi: 10.1073/pnas.0904792106.CrossRefGoogle Scholar
  11. 11.
    Chatterjee, D. K., & Yong, Z. (2008). Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells. Nanomedicine, 3(1), 73–82. doi: 10.2217/17435889.3.1.73.CrossRefGoogle Scholar
  12. 12.
    Salthouse, C., Hilderbrand, S., Weissleder, R., Mahmood, U. (2008). Design and demonstration of a small-animal up-conversion imager. Optics Express, 16(26), 21731–21737.CrossRefGoogle Scholar
  13. 13.
    Xiong, L.-Q., Chen, Z.-G., Yu, M.-X., Li, F.-Y., Liu, C., Huang, C.-H. (2009). Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors. Biomaterials, 30(29), 5592–5600.CrossRefGoogle Scholar
  14. 14.
    Rezwan, K., Meier, L. P., Gauckler, L. J. (2005). Lysozyme and bovine serum albumin adsorption on uncoated silica and AlOOH-coated silica particles: the influence of positively and negatively charged oxide surface coatings. Biomaterials, 26(21), 4351–4357. doi: 10.1016/j.biomaterials.2004.11.017.CrossRefGoogle Scholar
  15. 15.
    Dubertret, B., Skourides, P., Norris, D. J., Noireaux, V., Brivanlou, A. H., Libchaber, A. (2002). In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science, 298(5599), 1759–1762. doi: 10.1126/science.1077194.CrossRefGoogle Scholar
  16. 16.
    Torchilin, V. P. (2004). Targeted polymeric micelles for delivery of poorly soluble drugs. Cellular and Molecular Life Sciences, 61(19), 2549–2559.CrossRefGoogle Scholar
  17. 17.
    Rapoport, N. (2004). Combined cancer therapy by micellar-encapsulated drug and ultrasound. International Journal of Pharmaceutics, 277(1–2), 155–162.MathSciNetCrossRefGoogle Scholar
  18. 18.
    Nishiyama, N., Bae, Y., Miyata, K., Fukushima, S., Kataoka, K. (2005). Smart polymeric micelles for gene and drug delivery. Drug Discovery Today Technologies, 2(1), 21–26.CrossRefGoogle Scholar
  19. 19.
    Ungun, B., Prud'homme, R. K., Budijon, S. J., Shan, J., Lim, S. F., Ju, Y., et al. (2009). Nanofabricated upconversion nanoparticles for photodynamic therapy. Optics Express, 17(1), 80–86.CrossRefGoogle Scholar
  20. 20.
    Gindy, M. E., & Prud'homme, R. K. (2009). Multifunctional nanoparticles for imaging, delivery and targeting in cancer therapy. Expert Opinion on Drug Delivery, 6(8), 865–878. doi: 10.1517/17425240902932908.CrossRefGoogle Scholar
  21. 21.
    Hu, H., Yu, M., Li, F., Chen, Z., Gao, X., Xiong, L., et al. (2008). Facile epoxidation strategy for producing amphiphilic up-converting rare-earth nanophosphors as biological labels. Chemistry of Materials, 20(22), 7003–7009. doi: 10.1021/cm801215t.CrossRefGoogle Scholar
  22. 22.
    Roullier, V., Grasset, F., Boulmedais, F., Artzner, F., Cador, O., Vr, M.-A. (2008). Small bioactivated magnetic quantum dot micelles. Chemistry of Materials, 20(21), 6657–6665. doi: 10.1021/cm801423r.CrossRefGoogle Scholar
  23. 23.
    Boulmedais, F., Bauchat, P., Brienne, M. J., Arnal, I., Artzner, F., Gacoin, T., et al. (2006). Water-soluble pegylated quantum dots: from a composite hexagonal phase to isolated micelles. Langmuir, 22(23), 9797–9803. doi: 10.1021/la061849h.CrossRefGoogle Scholar
  24. 24.
    Amela-Cortes, M., Roullier, V., Wolpert, C., Neubauer, S., Kessler, H., Bedel, O., Mignani, S., Marchi-Artzner, V. (2011). Stable functionalized PEGylated quantum dots micelles with a controlled stoichiometry. Chemical Communications, 47, 1246–1248.CrossRefGoogle Scholar
  25. 25.
    Reischl, D., & Zimmer, A. (2009). Drug delivery of siRNA therapeutics: potentials and limits of nanosystems. Nanomedicine: Nanotechnology, Biology and Medicine, 5(1), 8–20. doi: 10.1016/j.nano.2008.06.001.CrossRefGoogle Scholar
  26. 26.
    Hu, L., Mao, Z., Gao, C. (2009). Colloidal particles for cellular uptake and delivery. Journal of Materials Chemistry, 19(20), 3108–3115.CrossRefGoogle Scholar
  27. 27.
    Liu, J., Bauer, H., Callahan, J., Kopecková, P., Pan, H., Kopecek, J. (2010). Endocytic uptake of a large array of HPMA copolymers: elucidation into the dependence on the physicochemical characteristics. Journal of Controlled Release, 143(1), 71–79. doi: 10.1016/j.jconrel.2009.12.022.CrossRefGoogle Scholar
  28. 28.
    Decristoforo, C., Faintuch-Linkowski, B., Rey, A., von Guggenberg, E., Rupprich, M., Hernandez-Gonzales, I., et al. (2006). [99mTc]HYNIC-RGD for imaging integrin alphavbeta3 expression. Nuclear Medicine and Biology, 33(8), 945–952.CrossRefGoogle Scholar
  29. 29.
    Felding-Habermann, B., Fransvea, E., O'Toole, T., Manzuk, L., Faha, B., Hensler, M. (2002). Involvement of tumor cell integrin αvβ3 in hematogenous metastasis of human melanoma cells. Clinical & Experimental Metastasis, 19(5), 427–436. doi: 10.1023/a:1016377114119.CrossRefGoogle Scholar
  30. 30.
    Hosotani, R., Kawaguchi, M., Masui, T., Koshiba, T., Ida, J., Fujimoto, K., et al. (2002). Expression of integrin [alpha]V[beta]3 in pancreatic carcinoma: relation to MMP-2 activation and lymph node metastasis. Pancreas, 25(2), e30–e35.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sounderya Nagarajan
    • 1
    • 2
    Email author
  • Victor Roullier
    • 2
  • Marian Amela Cortes
    • 2
  • Muthu Kumara Gnanasamandham
    • 1
  • Aurélien Dif
    • 2
  • Fabien Grasset
    • 2
  • Yong Zhang
    • 1
    • 3
  • Valerie Marchi
    • 2
    Email author
  1. 1.Division of BioengineeringNational University of SingaporeSingaporeSingapore
  2. 2.Université de Rennes 1, Sciences Chimique de RennesRennes CedexFrance
  3. 3.Nanoscience and Nanotechnology InitiativeNational University of SingaporeSingaporeSingapore

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