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Cooperet al. Nanoparticles for radiation therapy FIGURE2 |Schematicofphotodynamic therapyand radiotherapy-photodynamic therapy“hybrid”approach. (A) In photodynamic therapy,photosensitizerdyemoleculescollectpreferentially inmalignantor inflamed tissue.Light isused toexcite thedye,generating reactiveoxygenspecieswhich lead tocell killing. (B) In the“hybrid” approach, ionizing radiation isused toexcitescintillatingnanoparticles, whichmaybe locateddeepwithin tissue.Thenanoparticles transferenergy toattachedphotosensitizermolecules,generatingROSandkillingcellsby thesamemechanismasphotodynamic therapy. materials, thishasnot yetbeenattempted. Someof thematerials alsoshowspecificchemicalchallengesaswewilldiscussinSection Biocompatibilityof lanthanide-basedmaterials. SCINTILLATION Scintillation, or radioluminescence (RL), is the processwhereby a material, referred to as a scintillator, produces light upon interaction with ionizing radiation. Inorganic nanoparticles (NPs) dopedwith lanthanides present an attractive, radiostable alternative toquantumdots for scintillation. Introduction to lanthanideluminescence Lanthanides arewell known for the luminescence of their triva- lent cations, which emit primarily through phosphorescence resulting from electronic transitions within the 4f shell (Bünzli and Eliseeva, 2010). Because these transitions are “forbidden” by Laporte’s parity selection rule (formally prohibiting electric dipole transitionsbetween states that conserveparity), theyhave low absorption cross-sections and their photoluminescence is commonly sensitized by Ce3+ (for downconversion, with Tb3+ acceptor)orYb3+ (forupconversion,withTm3+,Er3+,andHo3+ acceptors), thoughmore complex combinations of lanthanides are certainly possible. The efficiency of both processes benefits FIGURE3 |Photosensitizers. (A)Typical photosensitizer structures: mono-L-aspartyl chlorine6 (Talaporfinsodium), aPDTdrug that canbe isolated fromalgaeorgreenplants (approved inJapanand inPhase III trials in theU.S.); deuteroporphyrin IX, acandidatephotosensitizerwithseveral possiblederivatives. (B)Absorbancespectraofdifferent concentrationsof deuterophorphyrin IXdisulfonicacid (DPIX-DS).Note thestrengthof the Soretband (UV-blue) compared to thepeaks in the redder regions. froma lowphonon energy host, though is of increasing impor- tance for lower energy transitions. In the case of upconverting NPs, hexagonal phase (βphase)NaYF4 or isostructuralNaGdF4 aregenerally thepreferredhostmaterials. Themechanismofceriumluminescence isdistinct frommost other lanthanides.Neutral ceriumhasa [Xe]4f15d16s2 electronic configuration; in solution or in solid hosts, the+3 or+4 oxi- dation states are themost common.Only the+3 state is lumi- nescent, though the +4 state also has important implications for redox activity. In the+3 state, the 6s and 5d electrons are lost, leavingoneoptically active electron in the shielded4f shell. Fluorescence( S=0)arises fromparity-allowed,highoscillator strength 4f-5d transitions. Because the 5d orbitals are external, these transitions are sensitive to the crystal field, and vary in energyacross a substantial rangedependingon thehostmaterial (Dorenbos,2000). Cerium-dopedlanthanumfluoride(CexLa1−xF3)showslumi- nescence in the UV-blue (corresponding well to the Soret band) and so is a likely candidate for useful energy transfer to photosensitizers. Mechanismsofscintillation RLmechanisms of bulk CexLa1−xF3 crystals were elucidated in the late 80s and early-to-mid 90s as candidates for radiation www.frontiersin.org October2014 |Volume2 |Article86 | 52