Page - 54 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Cooperet al. Nanoparticles for radiation therapy fromLuBO3:Ce nanocrystals has been reported, with a consid- erable dependence on theNCdimensions (Klassen et al., 2008, 2009). NC grain sizes were controlled by altering annealing temperatures, and scintillation yields were found to increase dramatically for NCs ∼95nm in diameter, with roughly three times the intensity of NCs either 25nm larger or smaller. This is in contrast to LuF3:Ce NPs in the same size range, which exhibitedamonotonic sizedependence. Synthesis techniques and post-synthesis processing affect the size, crystallinity, anddopantdistributionofnanostructures.The role of post-synthesis annealing on NCs was recently investi- gatedwith LaPO4:Eu andLaPO4:Pr (Malyy et al., 2013), aswell as LuPO4:Ce (Vistovskyy et al., 2014). In the case of LaPO4:Ln, annealingwasused to increase the sizeof theNCs, also resulting in a change of lattice symmetry above∼500◦C.The subsequent effects on excitation processes over the range of 4–40eV are described in some detail. Across the energy range investigated, the distinct mechanisms include intracenter excitation, charge transfer excitation, exciton or e-h pair creation, electronic exci- tation multiplication (E > 2 Eg), or combinations (Figure4), and different sensitivities were shown for the two activators— thefirst stageofEu3+ recombination involving electroncapture, in contrast to hole capture byPr3+.WithLuPO4:Ce, substantial differences in the low energy (4–25eV) VUV excitation spec- trum and PL and RL decay kinetics were observed after the NCs were annealed for 2h at 1200◦C (vs. at 800◦C, 300◦C, or unannealed), corresponding to an increase in the crystallite size from3nm to 35nm.The increased size resulted inwell-defined PL emission components, dramatically enhanced band-to-band excitations above∼8.7eV, and the elimination of the slow RL decaycomponentascribedtosurfacedefects. Importantly, theRL intensityfor35nmNCswasfoundtobe∼100×strongerthanfor smaller(<12nm)NCs,whereasthePLintensityofbothtypeswas comparable. The synthesis and characterization of a number of Pr3+ and Ce3+-activated garnet, silicate and oxide nanoscintillators have recently been reported, with an emphasis on their use for combined XRT/PDT, in particular their emission in the 300–400nm range (Jung et al., 2014). The RL properties of powdered nanocrystalline samples prepared through combus- tion synthesis and annealing at 1200◦C were compared with single/microcrystallinesamplesofsimilarcompositions.Thegen- eral composition (Y1−xPrx)3Al5O12 [or yttrium aluminumgar- net (YAG):Pr, with an average diameter of 80nm] was found to have the highest scintillation yield of the nanoscintilla- tors tested under 50keV excitation, though with a different activator concentration dependence than single crystal sam- ples: quenching was observed for x > 1%, compared to x= 0.16–0.65% reported for single crystals. Somewhat surprisingly, only YAG:Pr NCs with x=0.75, 1, and 1.5% had greater emission intensity than Bi4Ge3O12 (BGO) NCs, in stark con- trast to single crystals, where BGO had the lowest relative intensity of the compositions investigated. Indeed, because the RL behavior of NCs is dependent on activator concentration quenching, which is in turn dependent on the NC compo- sition, size and crystallinity, it was suggested that the prop- erties of different preparations will likely have to be evalu- ated individually rather than predicted by bulk trends. The introduction of the article also provides an inclusive overview of recent progress in nanoscintillator research for biomedical applications. Nanoscintillators that do not emit through specific activa- tor ions are referred to as self-activated (SA), with lumines- cencearisingfromcore-valencetransitions, self-trappedexcitons, FIGURE4 |Mechanismsofscintillation inPr3+orEu3+-dopedLaPO4, dependingonexcitationenergy. (A) Intracenter (direct) excitationofLn activators. (B)Excitationbycharge transfer fromO2− toEu3+. (C)Direct exciton formation. (D)Creationofe-hpairs. (E)Excitationmultiplication,with secondaryexcitationas in (B). (F)Excitationmultiplication,withsecondary excitationas in (C). (G)PhotonswithE>Eg can result inexcitation multiplication involving thecreationofsecondarye-hpairs.Arrows: (1) Transitiondue tophotonabsorption. (2)Energyexchangedue to inelastic scatteringonvalencebandelectrons, and (3) relaxationofprimaryelectrons. (Reprintedwithpermission fromMalyyet al., 2013). www.frontiersin.org October2014 |Volume2 |Article86 | 54