Seite - 55 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Cooperet al. Nanoparticles for radiation therapy charge-transfer emissionsor othermechanisms.YAG,BaF2, and Y2O3 are among those that have been adapted to thenanoscale, but have not yet been investigated to a large extent as SA nanoscintillators. These compositions are also routinely doped withotheractivators, resultinginvariouseffectsontheir intrinsic luminescence. BIOCOMPATIBILITYOFLANTHANIDE-BASEDMATERIALS Preparation of LnNP bioconjugates (covalent attachment of organicmolecules of interest to theNP surface ligands) appears infrequently in the literature. The principles of bioconjugation are similar to those forQDs, Au, or otherNPs, with some dis- tinct stability and solubility concerns (Cao et al., 2012; Jiang et al., 2012). Ligand-exchanged and silicated LnNPs typically presentprimaryamine functionalitieswhichprovide someaddi- tionalversatilityovercarboxylgroups.Aminesprovideanumber of conjugation routes, including routine reactions with amine, isothiocyanate,carboxyl,hydroxyl,andthiolfunctionalgroupson amoleculeofinterest.Onestudyreportedconjugatesofphospho- rylethanolamine (PEA)-stabilized Eu3+ and Ce3+/Tb3+-doped LaF3byreactingthefreeamineoftheligandwithactivatedbiotin- PEG ormPEGNHS esters, demonstrating a successful strategy forattachmentofmolecules throughamidebondformation.The use of these conjugates was restricted to borate buffer. Biotin conjugates have also been preparedwithCeF3:TbNPs silanized using TEOS/aminopropyltriethoxysilane (APTES) (Kong et al., 2007,2008a)andPEA-stabilizedLn3+-dopedzirconia (Liuet al., 2012). SCINTILLATINGNANOPARTICLEINTERACTIONSWITHDYESAND PHOTOSENSITIZERS(PSs) When nanoparticles are conjugated to PS molecules and irra- diatedwith ionizing radiation, singlet oxygen yield will depend upon scintillation yield and energy transfer efficiency. Neither of these parameters has been widely reported in the literature. However,agoodnumberof studieshave investigated lanthanide- dye charge transfer using light excitation, anda few studies have lookedat singletoxygengeneration. Lanthanide energy and charge transfer (ET and CT) have been extensively studied for lanthanide chelates andorganic dye pairs (Selvin, 1996, 2002), andmore recently in LnNPs, though most efforts have focused on sensitization of 4f-4f lumines- cence by Ce3+, Yb3+ or surface-associated organic molecules. The situation can quickly become rather complex with lan- thanides whose luminescence involves the 4fn configuration. In these cases, magnetic dipole transitions are allowed and may have intensity of the sameorder ofmagnitude as electric dipole transitions. Additionally, some induced dipole transitions are hypersensitive to the environment of the lanthanide ion and apparently follow the selection rulesof electric quadrupole tran- sitions, leading them to be referred to as pseudo-quadrupolar transitions. A2004reportinvestigatedenergytransferbetweenporousnet- works of interconnected 18nm YAG:Ce3+ nanocrystals (NCs) and the amine-reactive fluorescent dye tetramethylrhodamine isothiocyanate (TRITC) (Wuister et al., 2004).Glycinewas used to coat the NCs, bound to the surface through the carboxy- late moieties and providing terminal amines for attachment of TRITC. ET for the conjugate was demonstrated through strong emissionofTRITC relative toNCs following selective excitation of the NCs, as well as the appearance of a fast initial decay of the time-resolvedPL.TheETwasestimatedusingFörster-Dexter theory, giving a “critical distance” (equivalent to R0) of 7nm, resulting in energy transfer rates of up to 108 s−1 forCe3+ sites within5nmof theNCsurface, supposedtobe∼90%of the total Ce3+ giventheNCsize. Electrostatic complexes of CePO4:Tb nanorods and Rhodamine B (RhB), using Ce3+-sensitized Tb3+ emission to excite RhB, resulted in ET efficiency η up to 0.85 as deter- mined by ratiometric luminescence analysis (Di et al., 2010). EvidenceofETwastakenbythequenchingoftheNPsteady-state luminescence and concomitant increase in RhB emission with increasing amounts ofRhB.Time-resolvedmeasurements of the 5D4→7F5 transition of Tb3+ also exhibited quenching but did not quantitatively agree, reporting efficiencies lower than those determined by steady-state quenching (η ∼ 0.7 at the highest quenchingcondition). A recent (2013) study investigated electrostatic complexes of LaPO4:Ce nanorods and the fluorescent dye coumarin 440 (C-440) using steady-state and time-resolved PLmeasurements (Kar et al., 2013). The Stern-Volmer sphere of action static quenchingmodelwasapplied to the steady-statequenching, and theETefficiency estimatedby the ratioof theCe3+fluorescence lifetimes, giving η=0.24 for an estimated 1:47 nanorod:dye ratio. ET was corroborated by an increase of the fluorescence lifetimeof the dye, excited at 280nm,when complexedwith the nanorods. X-ray-induced singlet oxygen production has been inves- tigated with a handful of Tb3+-activated oxide and fluoride nanoscintillators coupled with grafted or encapsulated pho- tosensitizers. In one study, 11-aminoundecanoic acid-coated La0.8Tb0.2F3 NPs were mixed with the water-soluble photo- sensitizer meso-tetra(4-carboxyphenyl) porphine (MTCP) (Liu et al., 2008), which resulted in an increase in the quenching rate of the anthracenedipropionic acid (ADPA) singlet oxygen probe compared toPS alone under 250keVX-ray irradiation at 44cGy/min. Singlet oxygenproductionwas demonstrated using (Gd0.5Tb0.5)2O3 NPs with PS-encapsulating polysiloxane shells (Seve et al., 2012). The photosensitizer 5-(4-carboxyphenyl)- 10,15,20-triphenyl-chlorin (TPC)wasfirst conjugated toAPTES beforereactionoftheTPC-APTESwithTEOSforshellformation, resulting invaried amountsof covalently boundTPCembedded within the shell. In this case, increasingconcentrationsof encap- sulatedTPCresultedinquenchingoftheTPCPL(directlyexcited at414nm)aswellas singletoxygenproduction(directlydetected through 1270nm phosphorescence). This result was attributed tomigrationof excitationenergybetweenTPCmolecules termi- natedatstaticquenchingsites,withamodeldevelopedtosupport thedata. Recently, energy transfer mechanisms and singlet oxygen production under optical and X-ray irradiation were stud- ied using a similar system consisting of Gd-free Tb2O3 NPs with thephotosensitizer5-(4-carboxyphenyl)-10,15,20-triphenyl Frontiers inChemistry | ChemicalEngineering October2014 |Volume2 |Article86 | 55