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The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

Nature Materials volume 13, pages 418–426 (2014)Cite this article

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Abstract

Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

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Figure 1: Optical properties of ZGO.
Figure 2: In vivo imaging with ZGO-based PLNPs.
Figure 3: In vivo comparison of negatively charged QDs and PLNPs.
Figure 4: The surface functionalization and characterization of red-excitable PLNPs.
Figure 5: The biodistribution of stealth ZGO–PEG nanoparticles in tumour-bearing mice (n = 3).
Figure 6: Cellular tracking with persistent luminescence after LED excitation.

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Acknowledgements

We thank R. Lai-Kuen and B. Saubamea (from the Technical Platform of IFR71/IMTCE–Cellular & Molecular Imaging), L. Binet (for electron paramagnetic resonance experiments), K. R. Priolkar and N. Basavaraju (for bulk ZGO samples), C. Charrueau and N. Neveux (for biomarker dosage) and S. Maitrejean (for ZGO and QD experiment comparison). This work has been supported by the French National Agency (ANR) (NATLURIM project ANR-08-NANO-025) and IFCPAR/CEFIPRA (Indo-French Center for the Promotion of Advanced Research).

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Authors and Affiliations

  1. Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS); UMR 8258 CNRS; U 1022 Inserm; Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, F-75270 cedex 06, France; Chimie-ParisTech,

    Thomas Maldiney, Johanne Seguin, Eliott Teston, Michel Bessodes, Daniel Scherman & Cyrille Richard

  2. UMR 8258 CNRS, Paris F-75231 cedex 05, France

    Thomas Maldiney, Johanne Seguin, Eliott Teston, Michel Bessodes, Daniel Scherman & Cyrille Richard

  3. Institut de Recherche de Chimie-Paris: UMR 8247 CNRS; Chimie-ParisTech,

    Aurélie Bessière, Suchinder K. Sharma, Bruno Viana & Didier Gourier

  4. Chimie-ParisTech, Paris F-75231 cedex 05, France

    Aurélie Bessière, Suchinder K. Sharma, Bruno Viana & Didier Gourier

  5. Faculty of Applied Sciences, Delft University of Technology, 2629 JB Delft, The Netherlands

    Adrie J. J. Bos & Pieter Dorenbos

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  1. Thomas Maldiney
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Contributions

T.M., B.V., D.G., D.S. and C.R. conceived and designed the research. T.M., J.S., E.T. and S.K.S. carried out the experiments. T.M., J.S., E.T. and D.S. were responsible for biological characterization and small animal in vivo imaging. T.M., A.B., S.K.S., B.V. and D.G. were responsible for optical and TSL characterization and mechanism, A.J.J.B. and P.D. were responsible for the TSL excitation spectra. All of the authors analysed the data and discussed the results. T.M., A.B., B.V., D.G., D.S. and C.R. wrote the manuscript. The authors declare no conflict of interest.

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Correspondence to Daniel Scherman or Cyrille Richard.

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Maldiney, T., Bessière, A., Seguin, J. et al. The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells. Nature Mater 13, 418–426 (2014). https://doi.org/10.1038/nmat3908

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