CeF3-ZnO scintillating nanocomposite for self-lighted photodynamic therapy of cancer

  • Tiziano Rimoldi
  • Davide Orsi
  • Paola Lagonegro
  • Benedetta Ghezzi
  • Carlo Galli
  • Francesca Rossi
  • Giancarlo Salviati
  • Luigi Cristofolini
Engineering and Nano-engineering Approaches for Medical Devices Original Research
Part of the following topical collections:
  1. Engineering and Nano-engineering Approaches for Medical Devices


We report on the synthesis and characterization of a composite nanostructure based on the coupling of cerium fluoride (CeF3) and zinc oxide (ZnO) for applications in self-lighted photodynamic therapy. Self-lighted photodynamic therapy is a novel approach for the treatment of deep cancers by low doses of X-rays. CeF3 is an efficient scintillator: when illuminated by X-rays it emits UV light by fluorescence at 325 nm. In this work, we simulate this effect by exciting directly CeF3 fluorescence by UV radiation. ZnO is photo-activated in cascade, to produce reactive oxygen species. This effect was recently demonstrated in a physical mixture of distinct nanoparticles of CeF3 and ZnO [Radiat. Meas. (2013) 59:139–143]. Oxide surface provides a platform for rational functionalization, e.g., by targeting molecules for specific tumors. Our composite nanostructure is stable in aqueous media with excellent optical coupling between the two components; we characterize its uptake and its good cell viability, with very low intrinsic cytotoxicity in dark.


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

10856_2016_5769_MOESM1_ESM.pdf (1.1 mb)
Supplementary Information


  1. 1.
    Juzenas P, Chen W, Sun Y-P, Coelho MAN, Generalov R, Generalova N, et al. Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. Adv Drug Deliv Rev. 2008;60:1600–14.CrossRefGoogle Scholar
  2. 2.
    Dolmans DEJGJ, Fukumura D, Jain RK. TIMELINE: Photodynamic therapy for cancer. Nat Rev Cancer 2003;3:380–7.CrossRefGoogle Scholar
  3. 3.
    Bonnett R. Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy. Chem Soc Rev. 1995;24:19CrossRefGoogle Scholar
  4. 4.
    Chen W, Zhang J Using nanoparticles to enable simultaneous radiation and photodynamic therapies for cancer treatment. J Nanosci Nanotechnol. 2006;6:1159–66.CrossRefGoogle Scholar
  5. 5.
    Liu Y, Chen W, Wang S, Joly AG. Investigation of water-soluble X-ray luminescence nanoparticles for photodynamic activation. Appl Phys Lett. 2008;92:043901.CrossRefGoogle Scholar
  6. 6.
    Lal S, Clare SE, Halas NJ Nanoshell-enabled photothermal cancer therapy: impending clinical impact. Acc Chem Res. 2008;41:1842–51.CrossRefGoogle Scholar
  7. 7.
    Llusar M, Sanchez C. Inorganic and hybrid nanofibrous materials templated with organogelators. Chem Mater. 2008;20:782–820.CrossRefGoogle Scholar
  8. 8.
    Zou X, Yao M, Ma L, Hossu M, Han X, Juzenas P, et al. X-ray-induced nanoparticle-based photodynamic therapy of cancer. Nanomedicine 2014;9:2339–51.CrossRefGoogle Scholar
  9. 9.
    Clement S, Deng W, Camilleri E, Wilson BC, Goldys EM. X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield. Sci Rep. 2016;6:19954.CrossRefGoogle Scholar
  10. 10.
    Rossi F, Bedogni E, Bigi F, Rimoldi T, Cristofolini L, Pinelli S, et al. Porphyrin conjugated SiC/SiOx nanowires for X-ray-excited photodynamic therapy. Sci Rep. 2015;5:7606CrossRefGoogle Scholar
  11. 11.
    SOSG kit, produced by Molecular Probes and commercialized by Life Technologies, product information: “Singlet Oxyg. Sens. Green Reagent”, Revis. 30/01/2004, Accessed 2 May 2016.
  12. 12.
    Kuimova MK, Yahioglu G, Ogilby PR. Singlet Oxygen in a Cell: Spatially Dependent Lifetimes and Quenching Rate Constants. J Am Chem Soc. 2009;131:332–40.CrossRefGoogle Scholar
  13. 13.
    Gai S, Yang P, Li X, Li C, Wang D, Dai Y, et al. Monodisperse CeF3, CeF3:Tb3+, and CeF3:Tb3+@LaF3 core/shell nanocrystals: synthesis and luminescent properties. J Mater Chem. 2011;21:14610.CrossRefGoogle Scholar
  14. 14.
    Clement S, Deng W, Drozdowicz-Tomsia K, Liu D, Zachreson C, Goldys EM. Bright, water-soluble CeF3 photo-, cathodo-, and X-ray luminescent nanoparticles. J Nanoparticle Res. 2015;17:7CrossRefGoogle Scholar
  15. 15.
    Zhu L, Li Q, Liu X, Li J, Zhang Y, Meng J, et al. Morphological control and luminescent properties of CeF3 nanocrystals. J Phys Chem. C 2007;111:5898–903.CrossRefGoogle Scholar
  16. 16.
    Moses WW, Derenzo SE. Cerium fluoride, a new fast, heavy scintillator. IEEE Trans Nucl Sci. 1989;36:173–6.CrossRefGoogle Scholar
  17. 17.
    Jacobsohn LG, Sprinkle KB, Roberts SA, Kucera CJ, James TL, Yukihara EG, et al. Fluoride nanoscintillators. J Nanomater. 2011;2011:1–6.CrossRefGoogle Scholar
  18. 18.
    Sakthivel S, Neppolian B, Shankar MV, Arabindoo B, Palanichamy M, Murugesan V. Solar photocatalytic degradation of azo dye: comparison of photocatalytic efficiency of ZnO and TiO2. Sol Energy Mater Sol Cells. 2003;77:65–82.CrossRefGoogle Scholar
  19. 19.
    Villani M, Rimoldi T, Calestani D, Lazzarini L, Chiesi V, Casoli F, et al. Composite multifunctional nanostructures based on ZnO tetrapods and superparamagnetic Fe3O4 nanoparticles. Nanotechnology 2013;24:135601.CrossRefGoogle Scholar
  20. 20.
    Kolb HC, Sharpless KB. The growing impact of click chemistry on drug discovery. Drug Discov. Today 2003;8:1128–37.CrossRefGoogle Scholar
  21. 21.
    Mitra S, S B, Patra P, Chandra S, Debnath N, Das S, et al. Porous ZnO nanorod for targeted delivery of doxorubicin: in vitro and in vivo response for therapeutic applications. J Mater Chem. 2012;22:24145.CrossRefGoogle Scholar
  22. 22.
    Pan J, Sun S-K, Wang Y, Fu Y-Y, Zhang X, Zhang Y, et al. Facile preparation of hyaluronic acid and transferrin co-modified Fe3O4 nanoparticles with inherent biocompatibility for dual-targeting magnetic resonance imaging of tumors in vivo. Dalt Trans. 2015;44:19836–43.CrossRefGoogle Scholar
  23. 23.
    Sahi S, Chen W. Luminescence enhancement in CeF3/ZnO nanocomposites for radiation detection. Radiat Meas. 2013;59:139–43.CrossRefGoogle Scholar
  24. 24.
    Sun Z, Li Y, Zhang X, Yao M, Ma L, Chen W. Luminescence and Energy transfer in water soluble CeF3 and CeF3:Tb3+ nanoparticles. J Nanosci Nanotechnol. 2009;9:6283–91.CrossRefGoogle Scholar
  25. 25.
    Haldar KK, Sen T, Patra A. Au@ZnO core-shell nanoparticles are efficient energy acceptors with organic dye donors. J Phys Chem. C 2008;112:11650–6.CrossRefGoogle Scholar
  26. 26.
    Kovács M, Valicsek Z, Tóth J, Hajba L, Makó É, Halmos P, et al. Multi-analytical approach of the influence of sulphate ion on the formation of cerium(III) fluoride nanoparticles in precipitation reaction. Colloids Surfaces A Physicochem Eng Asp. 2009;352:56–62.CrossRefGoogle Scholar
  27. 27.
    Sun Z, Li Y, Zhang X, Yao M, Ma L, Chen W. Luminescence and energy transfer in water soluble CeF3 and CeF3:Tb3+ nanoparticles. J Nanosci Nanotechnol. 2009;9:6283–91.CrossRefGoogle Scholar
  28. 28.
    Bauman RP, Porto SPS. Lattice vibrations and structure of rare-earth fluorides. Phys Rev. 1967;161:842–7.CrossRefGoogle Scholar
  29. 29.
    Sato-Berrú RY, Vázquez-Olmos A, Fernández-Osorio AL, Sotres-Martínez S. Micro-Raman investigation of transition-metal-doped ZnO nanoparticles. J Raman Spectrosc. 2007;38:1073–6.CrossRefGoogle Scholar
  30. 30.
    Wang YS, Thomas PJ, O’Brien P. Nanocrystalline ZnO with Ultraviolet Luminescence. J Phys Chem. B 2006;110:4099–104.CrossRefGoogle Scholar
  31. 31.
    Djurišić AB, Leung YH. Optical properties of ZnO nanostructures. Small. 2006;2:944–61.CrossRefGoogle Scholar
  32. 32.
    Porter KR, Todaro GJ, Fonte V. A scanning electron microscope study of surface features of viral and spontaneous transformants of mouse BALB/3T3 cells. J Cell Biol. 1973;59:633–42.CrossRefGoogle Scholar
  33. 33.
    Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature. 2003;422:37–44.CrossRefGoogle Scholar
  34. 34.
    Zhang S, Gao H, Bao G. Physical principles of nanoparticle cellular endocytosis. ACS Nano. 2015;9:8655–71.CrossRefGoogle Scholar
  35. 35.
    Popović ZV, Dohčević-Mitrović Z, Cros A, Cantarero A. Raman scattering study of the anharmonic effects in CeO 2− y nanocrystals. J Phys Condens Matter. 2007;19:496209.CrossRefGoogle Scholar
  36. 36.
    Porto SPS, Fleury Pa, Damen TC. Raman spectra of TiO2, MgF2, ZnF2, FeF2, and MnF2. Phys Rev. 1967;154:522–6.CrossRefGoogle Scholar
  37. 37.
    Irimpan L, Nampoori VPN, Radhakrishnan P, Deepthy A, Krishnan B. Size dependent fluorescence spectroscopy of nanocolloids of ZnO. J Appl Phys. 2007;102:063524.CrossRefGoogle Scholar
  38. 38.
    Riwotzki K, Meyssamy H, Schnablegger H, Kornowski A, Haase M. Liquid-phase synthesis of colloids and redispersible powders of strongly luminescing LaPO4:Ce,Tb nanocrystals. Angew Chemie Int Ed. 2001;40:573–6.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Physics and Earth Science DepartmentParma UniversityParmaItaly
  2. 2.IMEM-CNR InstituteParmaItaly
  3. 3.Biomedical, Biotechnological and Translational SciencesParma UniversityParmaItaly

Personalised recommendations