Published: June 24, 2011 r2011 American Chemical Society 11810 dx.doi.org/10.1021/ja204504w | J. Am. Chem. Soc. 2011, 133, 11810–11815 ARTICLE pubs.acs.org/JACS Controlling Electron Trap Depth To Enhance Optical Properties of Persistent Luminescence Nanoparticles for In Vivo Imaging Thomas Maldiney, † Aur  elie Lecointre, ‡ Bruno Viana,* ,‡ Aur  elie Bessi  ere, ‡ Michel Bessodes, † Didier Gourier, ‡ Cyrille Richard,* ,† and Daniel Scherman † † Unit  e de Pharmacologie Chimique et G en etique et d'Imagerie, CNRS, UMR 8151, Paris, F-75270 cedex France, Inserm, U1022, Paris, F-75270 cedex France, Facult  e des Sciences Pharmaceutiques et Biologiques, Universit  e Paris Descartes, Paris, F-75270 cedex France, and ENSCP, Chimie ParisTech, Paris, F-75231 cedex France ‡ Laboratoire de Chimie de la Mati  ere Condens ee de Paris, Ecole Nationale Sup erieure de Chimie de Paris (Chimie ParisTech), CNRS, UMR 7574, Paris, 75231 cedex 05, France b S Supporting Information ’ INTRODUCTION In vivo optical imaging, using photons as primary information, has witnessed several major improvements in the last decades. 1 Among a wide panel of very sensitive and efficient photonic probes, inorganic-based sensors, such as quantum dots (QDs), potentially offer the highest quantum efficiency through living tissue. 2 Yet genuinely intense, QDs emission requires continuous illumination and thereby suffers from significant background signal (autofluorescence) emitted from irradiated tissues. 3 To address this important issue, we reported the synthesis of persistent luminescence nanoparticles (PLNP) with the formula Ca 0.2 Zn 0.9 Mg 0.9 Si 2 O 6 :Eu 2+ ,Mn 2+ ,Dy 3+ (hereafter referred to as CZMSO:Eu,Dy) and sharing the same crystalline structure as diopside CaMgSi 2 O 6. 4 Such material possesses the ability to be excited under UV light before intravenous injection in mice, and to emit in the near-infrared window without further irradiation, circumventing autofluorescence from animal tissues. We have shown that PLNP could be used as a sensitive optical probe for in vivo imaging, and that their biodistribution was highly dependent on both core diameter and global surface charge. 5 However, luminescence from these PLNP was not intense enough to provide long-term monitoring of in vivo probe accumulation, unveiling the need to work on new nanomaterials with improved optical characteristics. To better understand the origin of such a phenomenon in the CZMSO lattice, and to ensure pure diopside crystalline structure, we have previously suggested a mechanism of persistent lumi- nescence in the diopside host, with Mn 2+ acting both as the hole trap and the recombination center. The X-ray induced thermally stimulated luminescence (TSL) measurements revealed that when Dy 3+ was added as a codoping ion, the red persistent luminescence was enhanced. 6 We then hypothesized that triva- lent lanthanide ions could act as an efficient electron trap for persistent luminescence. 7 Starting from the hypothesis that controlling electrons trap depth could help to enhance the optical properties of PLNP, 8 we presently report the synthesis of several Mn 2+ doped diopside nanoparticles, either codoped with trivalent lanthanide ions CaMgSi 2 O 6 :Mn 2+ ,Ln 3+ (Ln = Dy, Pr, Ce, Nd), only excitable with X-rays (hereafter referred to as CMSO:Ln), or tridoped with divalent europium and trivalent lanthanide ions CaMg- Si 2 O 6 :Mn 2+ ,Eu 2+ ,Ln 3+ , to enable UV excitation (hereafter re- ferred to as CMSO:Eu,Ln). These nanomaterials were compared to hybrid enstatiteÀdiopside CZMSO already used for in vivo imaging. Divalent manganese, present in all the compounds, is at Received: May 25, 2011 ABSTRACT: Focusing on the use of nanophosphors for in vivo imaging and diagnosis applications, we used thermally stimulated luminescence (TSL) measurements to study the influence of triva- lent lanthanide Ln 3+ (Ln = Dy, Pr, Ce, Nd) electron traps on the optical properties of Mn 2+ -doped diopside-based persistent lumi- nescence nanoparticles. This work reveals that Pr 3+ is the most suitable Ln 3+ electron trap in the diopside lattice, providing optimal trap depth for room temperature afterglow and resulting in the most intense luminescence decay curve after X-ray irradiation. This luminescence dependency toward the electron trap is maintained through additional doping with Eu 2+ , allowing UV-light excitation, critical for bioimaging applications in living animals. We finally identify a novel composition (CaMgSi 2 O 6 :Eu 2+ ,Mn 2+ ,Pr 3+ ) for in vivo imaging, displaying a strong near-infrared afterglow centered on 685 nm, and present evidence that intravenous injection of such persistent luminescence nanoparticles in mice allows not only improved but highly sensitive detection through living tissues.