Persistent luminescence nanoparticles have recently been proposed as innovative optical probes for small animal in vivo imaging. The main advantage of such probes is their ability to emit light for a long time after the end of their excitation, allowing in vivo imaging with low background. This work reports new information on the physico-chemical characterizations of Cr doped ZnGa<sub>2</sub>O<sub>4</sub> nanoprobes in terms of synthetic procedure, luminescence properties as well as colloidal stabilities in different aqueous media and over the time.
We presently introduce a novel generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated<i> in vivo </i>through living tissues using highly penetrating low energy photons from the red region of the visible spectrum. Surface functionalization of this photonic nanoprobe can be adjusted to favor multiple challenging biomedical applications.
Red emitting long-lasting phosphorescence (LLP) material, are useful biomarker for small animal in vivo imaging. We
report here our investigations on the optical features of chromium doped AB<sub>2</sub>O<sub>4</sub> spinels (A=Zn, Mg and B=Ga, Al…) suitable for such applications. It is possible to tune the emission wavelengths of Cr<sup>3+</sup> by a crystal field variation to be well centered in the biological window and it is also possible to adjust the traps depth in order to better control the release of the traps. These traps are therefore stable at room temperature and could be emptied by thermal or near
infrared source making this material a potential new photostimulated/optically compound. Photoluminescence (PL)
and thermally stimulated luminescence (TSL) studies are reported.
ZnGa<sub>2</sub>O<sub>4</sub> (ZGO) is a normal spinel. When doped with Cr<sup>3+</sup> ions, ZGO:Cr becomes a high brightness persistent luminescence material with an emission spectrum perfectly matching the transparency window of living tissues. It allows <i>in vivo</i> mouse imaging with a better signal to background ratio than classical fluorescent NIR probes. The most interesting characteristic of ZGO:Cr lies in the fact that its LLP can be excited with red light, well below its band gap energy and in the transparency window of living tissues. A mechanism based on the trapping of carriers localized around a special type of Cr<sup>3+</sup> ions namely Cr<sub>N2</sub> can explain this singularity. The antisite defects of the structure are the main responsible traps in the persistent luminescence mechanism. When located around Cr<sup>3+</sup> ions, they allow, via Cr<sup>3+</sup> absorption, the storage of not only UV light but also all visible light from the excitation source.
Last generation medical imaging equipments require materials which possess outstanding performances. For scintillators in the high energy imaging field (PET), crystals with high light yields allow a decrease of the irradiation dose received by the patients during medical application and a more accurate diagnostic. Thermally stimulated luminescence (TSL) data provides the depth of hole or electron traps which can limit the efficiency and increase the kinetic. If these traps are due to lanthanide ions, the level schemes can predict the depth values. Thanks to comparison between TSL glow curves and energy diagrams, the traps inside oxide-based-hosts can be identified. Two examples are proposed here, first, the scintillation in the Ce:LYSO crystals which can be improved by thermal annealing and where divalent cations are used for charge compensation and traps removal and second, optical imaging using a new approach where persistent luminescent nanoparticles are used for <i>in-vivo</i> imaging. In both cases, traps depth should be carefully controlled.
Regarding its ability to circumvent the autofluorescence signal, persistent luminescence was recently shown to be a
powerful tool for in vivo imaging and diagnosis applications in living animal. The concept was introduced with
lanthanide-doped persistent luminescence nanoparticles (PLNP), from a lanthanide-doped silicate host
Ca<sub>0.2</sub>Zn<sub>0.9</sub>Mg<sub>0.9</sub>Si<sub>2</sub>O<sub>6</sub>:Eu<sup>2+</sup>, Mn<sup>2+</sup>, Dy<sup>3+</sup> emitting in the near-infrared window. In order to improve the behaviour of these
probes in vivo and favour diagnosis applications, we showed that biodistribution could be controlled by varying the
hydrodynamic diameter, but also the surface charges and functional groups. Stealth PLNP, with neutral surface charge
obtained by polyethylene glycol (PEG) coating, can circulate for longer time inside the mice body before being uptaken
by the reticulo-endothelial system. However, the main drawback of this first generation of PLNP was the inability to
witness long-term monitoring, mainly due to the decay kinetic after several decades of minutes, unveiling the need to
work on new materials with improved optical characteristics. We investigated a modified silicate host, diopside
CaMgSi<sub>2</sub>O<sub>6</sub>, and increased its persistent luminescence properties by studying various Ln<sup>3+</sup> dopants (for instance Ce, Pr,
Nd, Tm, Ho). Such dopants create electron traps that control the long lasting phosphorescence (LLP). We showed that
Pr3+ was the most suitable Ln<sup>3+</sup> electron trap in diopside lattice, providing optimal trap depth, and resulting in the most
intense luminescence decay curve after UV irradiation. A novel composition CaMgSi<sub>2</sub>O<sub>6</sub>:Eu<sup>2+</sup>,Mn<sup>2+</sup>,Pr<sup>3+</sup> was obtained
for in vivo imaging, displaying a strong near-infrared persistent luminescence centred on 685 nm, allowing improved and
sensitive detection through living tissues.
Fluorescence is increasingly used for in vivo imaging and has provided remarkable results. Howerver this
technique presents several limitations, especially due to tissue autofluorescence under external illumination and weak
tissue penetration of low wavelength excitation light. We have developed an alternative optical imaging technique using
persistent luminescent nanoparticles suitable for small animal imaging. These nanoparticles can be excited before the
injection, and their in vivo distribution can be followed in real-time for several hours. Chemical modifications of their
surface is possible leading to lung or liver targeting, or to long-lasting blood circulation.