Nanoparticules à luminescence persistante pour l'imagerie optique in vivo

Size: px

Start display at page:

Download "Nanoparticules à luminescence persistante pour l'imagerie optique in vivo"

Corey Brown
5 years ago
Views:

1 Nanoparticules à luminescence persistante pour l'imagerie optique in vivo Cyrille RICHARD UPCGI, CNRS UMR8151, Inserm U1022 Université Paris Descartes Paris

2 What is persistent luminescence? CB ptical phenomenon in which the excitation light is stored in traps, and is then slowly released upon thermal activation, hv T Electron trap Emission producing a light emission which can last for several hours. VB

3 What is persistent luminescence? CB ptical phenomenon in which the excitation light is stored in traps, and is then slowly released upon thermal activation, hv T Electron trap Emission producing a light emission which can last for several hours. VB Main applications: traffic signs, emergency signage, watches, luminous paints, textile printing

4 Development of a new type of imaging probes Emission of light for several hours Probes excited before the injection _ no autofluorescence Emission of light in the tissue transparency window (> 650 nm) Nanometric size CNRS patent 2007, FR

5 State of the art Wang et al., J Lumin 2003, , A = CaAl 2 4 : Mn 2+, Ce 3+ B = Ca 2 Al 2 Si 7 : Mn 2+, Ce 3+ C = MgSi 3 : Eu 2+, Dy 3+, Mn 2+ Solid state synthesis A B C A B C

6 First generation of silicates for in vivo imaging Small particles: Sol-gel process MgSi 3 : Eu 2+, Dy 3+, Mn 2+ ZnMgSi 2 6 : Eu 2+, Dy 3+, Mn 2+ Ca 0,2 Zn 0,9 Mg 0,9 Si 2 6 : Eu 2+, Dy 3+, Mn 2+ ptical characteristics Intensity (a.u.) Time (s) ACS Nano 2011, 5,

7 Surface modifications of the nanoparticles H H Si Si H H Si Si H APTES DMF NH NH 2 2 NH NH 2 2 DMF DMF Me-PEG CH BP, TEA, DMF BP, TEA, DMF Si Si H H Si Si N NH H N NH H H H H H Carboxy-PLNP ZP ZP = mv mv Amino-PLNP Zeta Potential = +35 mv Si H Si N H N H n = 112 n = 112 CH 3 CH 3 PEG-PLNP ZP = 0 mv

8 Biodistribution of the chemically modified probes Dispersion in 150 mm NaCl Excitation for 2 minutes under UV light Injection in the tail vein Amino-PLNP Carboxy-PLNP PEG-PLNP PNAS, 2007, 104,

9 Mechanism of persistent luminescence Excitation light is stored by electrons traps, and is then slowly released upon thermal activation of emitting centres, producing a light emission. A. Bessière, B. Viana, D. Gourier, LCMCP electron hole CB conduction band; VB valence band Thermal activation

10 Influence of electron trap on persistent luminescence Synthesis of CMS: Eu 2+, Mn 2+, Ln 3+ (Ln 3+ = Ce 3+, Nd 3+, Pr 3+, Dy 3+ ) bservation of the different powders:

11 Comparative in vivo study of the two UV-excitable compositions CMS: Dy 3+ doped CMS: Pr 3+ doped JACS 2011, 133,

12 In vivo activation of persistent luminescence for long term imaging CNRS Patent, 2012, FR

13 Second generation of persistent luminescence nanoparticles: ZnGa 2 4 :Cr 3+ A. Bessière et al,. ptics Express, 2011, 19(11), ZnGa 2 4 :Cr 3+

14 Second generation of persistent luminescence nanoparticles: ZnGa 2 4 :Cr 3+ A. Bessière et al,. ptics Express, 2011, 19(11), ZnGa 2 4 :Cr 3+

15 Surface modification and biodistribution studies

16 Surface modification and biodistribution studies Biodistribution studies in healthy mice: 3 min 30 min 1h 2h 3h

17 Biodistribution studies in tumor bearing mice 1h 2h 4h 6h Nature Materials, under revision

18 Conclusion Persistent luminescence nanoparticles for in vivo imaging applications First generation: UV excitation Injection bservation Silicate Time scale 0 hours

19 Conclusion Persistent luminescence nanoparticles for in vivo imaging applications First generation: UV excitation Injection bservation Silicate Time scale 0 hours Second generation: Gallate UV excitation Injection bservation In vivo excitation Time scale 0 hours weeks

Acknowledgements PhD students: Quentin le Masne de Chermont (2004-2007) Thomas Maldiney (2009-2012) Collaborators: Johanne Seguin, Michel Bessodes, Daniel Scherman: UPCGI Bruno

20 Acknowledgements PhD students: Quentin le Masne de Chermont ( ) Thomas Maldiney ( ) Collaborators: Johanne Seguin, Michel Bessodes, Daniel Scherman: UPCGI Bruno Viana, Aurélie Bessière, Aurélie Lecointre, Didier Gourier: LCMCP Financial supports: Région Ile-de-France (In actio ) ANR PNAN (Natlurim ) EC (Clinigene, )

Persistent luminescence nanoparticles for bioimaging applications

Persistent luminescence nanoparticles for bioimaging applications Gonzalo Ramírez-García, 1,2 Fanny d rlyé, 1 Anne Varenne, 1 Nathalie Mignet, 1 Silvia Gutiérrez-Granados, 2 Minerva Martínez-Alfaro, 2