1 Lightsourcesfor photonanotechnology
SeokKiChoi
MichiganNanotechnologyInstituteforMedicineandBiologicalSciences, andDepartmentofInternalMedicine,UniversityofMichiganMedicalSchool, AnnArbor,MI,UnitedStates
OUTLINE
1.1Introduction1
1.2Basicpropertiesoflight2
1.2.1Absorption3
1.2.2Scattering3
1.2.3Penetration3
1.3Divisionoflightsources3
1.3.1Ultravioletlight4
1.3.2Visiblelight6
1.3.3Nearinfraredlight6
1.4Nanotechnologyforphototherapy: overview9
1.4.1Light-controlleddrugrelease10 1.4.2Photothermaltherapy10
1.4.3Photodynamictherapy13 1.5Summary14 Abbreviations14 Acknowledgments15 References15
1.1Introduction
Lighthastheabilitytoinduceoralterchemical,physical,orbiologicalactivitiesincertain classesofnanometer-sizedparticles(NPs)[ 1 8].SuchNPs,genericallyreferredtoasphotoactivenanomaterials,havemadesignifi cantcontributionstothecreationofnovelapplicationsanddevelopmentinnanotechnolog y.Theirapplicationsarehighlybene fi cialina
1.Lightsourcesforphotonanotechnology
rangeof fi eldsincludingenergy[9 ],chemicalcatalysis[9 ,10],sensors[9 , 11 ],therapeutics [7 ,12 14 ],imaging[ 15 ,16 ],anddiagnostics[17].
Lightplaysanactiveroleinservingasanexternalstimuluswithitssuperbtemporaland spatialcontrolcapabilities[18 21].Itcarriesabroadrangeofactivationenergy,whichis tunableforactivatingaspecificphotoactiveNPcoreoritsperipheralcomponenttoinduce light-inducedoutputsuchasscattering, fluorescence,andluminescence(Fig.1.1).Useoflight constitutesanessentialcomponentinNPdetectionandimagingmethods[22,23].Light absorptionoffersanumberofmechanismsthatallowforcontrolorinducementoftherapeuticeffects.TheserelatetoenablingthecontrolledreleaseofatherapeuticagentcarriedbyNP [7],inductionoflocalizedheatinphotothermaltherapy(PTT),orproductionofcytotoxic reactiveoxygenspecies(ROS)inphotodynamictherapy(PDT)[22 24].
Inadditiontosuchactivecontrol,usingalightstimulusoffersahighdegreeofprecisionin thespatiotemporalcontrolofNPactivation[7,18,21,25].Thesebene fitsarenotgenerally achievableinNPactivationtriggeredbyapassivestimulussuchasanendogenous,acellular, orapathophysiologicalfactor(lowpH,enzymes,andthiols)[7].Furthermore,lightstimulationoffershigherprecisioninthespatialresolutionoflightexposurethanothertypesof externalstimulibasedonheatorultrasound[26,27].
Incontrasttoitsbene ficialproperties,theapplicationoflightinnanotechnologyfaces certaindrawbacksdeterminedbytheintrinsicpropertiesoflight.ItisthuscriticaltounderstandlightpropertiesandconsiderintheearlyphasesofNPdesign.Thischapterdescribes lightsourceswithafocusonthreespectralregionsofrelevance ultraviolet(UV),visible (Vis),andnear-infrared(NIR) andtheirpropertiesandusesinlight-controlleddrug delivery,PDT,andPTT.
1.2Basicpropertiesoflight
Selectionoflightsourcesplaysafundamentalroleincontrollingthespeci ficfunctionsof photoactiveNPsbecauseonlyaspeci ficwavelengthoflightisbestabletotriggerorconfera desiredeffectsuchascleavingadrug-NPlinkerfordrugrelease,activatingaphotosensitizer moleculeforPDT,orexcitinga fluorescentmoleculeforopticalimaging(Fig.1.1).
FIGURE1.1 Photophysicalandphotochemicaleventsthatpertaintolightexposedtoaphotoactivenanoparticle (NP).
1.2.1Absorption
LightabsorptionbyasmallmoleculeoranNPoccursmostef ficientlyataparticularwavelengthoflightdictatedbyachromophoregroupconstitutingthemoleculeorpresentedinthe NPcore.ItslightabsorptionisdefinedaccordingtotheBeer Lambertlaw(A ¼ ε l c) [28]inwhich ε,l,andcrefertoitsmolarabsorptivity(molarextinctioncoef ficient,M 1 cm 1) atthespecificwavelengthoflight,thepathlengthoflight(cm),anditsconcentration(M), respectively.Thisrelatestheextentoflightabsorptiontothenumberandabsorptivityofmoleculesexposedalongthelightpath.
Underbiologicalconditions,watermoleculesareabundantlypresentinserum,bloodcells, andtissues,andtheycontributesignificantlytolightabsorption[29].Avarietyofmolecules/ macromoleculesofbiologicalabundancealsocontributetolightabsorptionandincludesmall pigmentmolecules,(oxy)hemoglobin,aminoacids,proteins,andnucleicacids[30].Thus, lightabsorptionoccurringbymoleculesinbiologicalmediaconstitutesaprimaryfactor thatcanadverselyinfluencetheef ficiencyoflightapplications inparticular,invivo[29].
1.2.2Scattering
LightscatteringoccurswhenitinteractswithNPsaswellasmacromolecularparticles, whichareabundantinbloodcells,skinpigments, fibers,andbones[31,32].Theextentoflight scatteringatagivenwavelength(l)variesnonlinearlytoatermofa (l/500nm) b withan inversecorrelationtob,inwhichaandbeachreferstoatissue-specificvalue[33].Ingeneral, thescatteringdecreasesasafunctionofwavelength(l),withhigherscatteringoccurringat theshorterUVandVislightwavelengthsthanatNIRwavelengths(Fig.1.2).Itisalsodependentontissuetypes,withhigherscatteringobservedinskinthaninsoftandfattytissues[33].
1.2.3Penetration
Duetolightscatteringandabsorption,onlyacertainfractionoflightisabletopass throughabiologicalsample,whileitsintensitynonlinearlydecreasesalongitspath (Fig.1.2).Theextentoflightpenetrationisgenerallydependentonlightwavelength [33 35].Lightpenetratesmoreeffectivelyatalongerwavelengththanashorterwavelength asschematicallyillustratedinamodelforhumanskinstructure[36].ComparedwithUVand Vis,NIRlight(800 1000nm)showsanabilityfordeeperpenetration,whichmakesita preferredsourceforopticalimaginginvivo.
1.3Divisionoflightsources
LightsourcesfrequentlyusedinimagingandtherapeuticactivationconsistofthreespectralregionsthatspanUV(200 400nm),Vis(400 800nm),andasubsectionofNIR (800 1000nm)(Fig.1.2).Eachoftheselightsourcesdisplaysadistinctsetofphotochemical andphotophysicalpropertiesthatvaryasafunctionofwavelength.
FIGURE1.2 Spectralrangeoflightsourcesfrequentlyusedinnanotechnology(top),andlightpropertiesassociatedwiththebiologicaltissue(bottom).
1.3.1Ultravioletlight
LightintheUVzoneissubdividedintothreeregionscomposedofshort(UVC, 100 280nm),medium(UVB,280 315nm),andlong(UVA,315 400nm)wavelengths. Theshortest,UVC,isthemostharmfultomammaliancellsbecauseofitsabilitytocause DNAdamage,whichmakesitrarelyusedinbiologicnanotechnology.However,itisbeneficialforcertainapplicationsbecauseofitsbroad-spectrumcidalityagainstbacterialpathogens.ThisisevidentfromthecurrentpracticeofusingUVCinlight-basedtherapytotreat woundinfections.Thisapplicationdoesnotinvolvetreatmentwithanantibacterialagent butirradiationalone[37].
ComparedwithUVC,thetwolongerUVlights(UVAandUVB)causeonlyinsignificant cellulartoxicity[38 40].Theycarryhigh-enoughenergyforimagingandtherapeuticapplicationsinnanotechnology.First, fluorescentimagingexperimentsonphotoactiveNPssuch asquantumdots(QDs)[41 43],grapheneoxide(GO)[44,45],andcarbondots(CDs)involve excitationatUVAandUVBwavelengths(Table1.1)[23,58].Second,theseUVlightsare frequentlyusedforROSproductioninthePDTapplicationofphotosensitizers(chlorine6 [59],protoporphyrinIX[51])andphotoactiveNPs(nano-TiO2 [60 62],nano-ZnO[63],GO nanosheet[64,65],andfullerene[66,67]).Third,theyplayanimportantroleinlightcontrolleddrugdeliveryasappliedinabroadrangeoftherapeuticagents(Table1.2)
TABLE1.1 Lightwavelengthsofrelevancetonanoparticleactivationandimaging.
lex (nm)PhotoresponsiveordyemoleculePhotoactivenanoparticle
300
400 AlexaFluor 405,488,568, 594,633
Chlorine6[59]; protoporphyrin IX
Fluorescein isothiocyanate; Hoescht33258; DAPI
QD(360 400nm) [41 43]
GQD (320nm) [44,45]
CD(330 475) [23,46]
500 Cyanine: Cy3,Cy5 Rhodamine;PI
600
700
800
Nano-Au,nano-Ag(500 800nm)[5,6,46,47]
UCN(808nm)[48 50];UCN (980nm)[14,48,49,51 53]
SWNT (808nm)[54]
900 1000 Metaloxide NP[55 57]
AuNP,goldnanoparticle; CD,carbondot; GQD,graphenequantumdot; NP,nanometer-sizedparticle(nanoparticle); QD,quantumdot; SWNT,single-walledcarbonnanotube; UCN,upconversionnanocrystal.
TABLE1.2 Typesofphotonanotherapyincludinglight-controlleddrugdelivery,photothermaltherapy,and photodynamictherapy.
l (nm)PayloadreleasePTTPDT
UVB254MTX[68]
300Phosphoramide[69]
UVA308 L-Glutamate[70]
347; 350 Choline[71];EGTA[72];glutamate[73 75]; oligonucleotide[76];tegafur[77];taxol[78]
365Ciprofloxacin[39];camptothecin[79];DOX[38,80]; doxycycline[81];5-FU[82]; glutamate-kinate[73,74];inositolphosphate[83]; MTX[68,84];TAM[20,85,86];taxol[78,87]; insulin[88]
Vis420Chlorambucil[89,90]
430Taxol[92]
690Duocarmycin[93];4-Hydroxycyclofen[96,97]
780Duocarmycin[93];4-hydroxytamoxifen[94]
NIRa 808Chlorambucil[89,90]
980Chlorambucil[97];DOX[14,40];Luciferin[98]; siRNA[99]
360 600nm Nano-TiO2 [60 62]; nano-ZnO[63]; graphene oxidenanosheet[64,65]; fullerene[66,67]
500 800nm nano-Au[5,6]; nano-Ag [46,47,91]
UCN(808nm)[50,53]; UCN(980nm) [14,27,51,53,95,96]
aMediatedbyUV VisemissionfromNIR-excitedupconversionnanocrystal(UCN); 5-FU,5-fluorouracil; DOX,doxorubicin; EGTA,egtazic acid; MTX,methotrexate; PDT,photodynamictherapy; PTT,photothermaltherapy; TAM,tamoxifen.
[7,23,100,101].Theseincludeanticanceragentssuchasdoxorubicin(DOX)[38,80],5-FU[82], methotrexate[68,84],paclitaxel(taxol)[78,87],camptothecin[79],tamoxifen[20,85,94],antibacterialagentssuchasciprofloxacin[39],andinsulin[88].
Inspiteofsuchwideutility,usingUVlightisnotfreefromunfavorableproperties,particularlyinvivo.ItundergoeslightscatteringtoanextentgreaterthanforlongerVisorNIR light(Fig.1.2).Itshowsabsorptionbymostbiologicalmoleculespresentinbloodandtissues, inparticularinyellowpigments(bilirubin, b-carotene)and(oxy)hemoglobinmolecules[33]. UVabsorptionbythesepigmentsandmoleculesispartlyresponsibleforthelowerlevelof tissuepenetrationthanoccurswithVisandNIR.Forexample,shortandmediumUVlight showspoorskinpenetration(w2 mm)[36,102].LongUVAshowsagreaterlevelofpenetration,asdeepas60 90 mmat350 400nm[36,102].NumerousUVAapplicationshavebeen demonstratedinvivoforUVA-mediateddrugactivationorimagingstudies[103].
1.3.2Visiblelight
LightintheVisregioncompriseswavelengthsfrom400nm(violet)to800nm(red) (Fig.1.2).Vislightoffersapromisingopportunitywithitssigni ficantlyincreasedtissuepenetrationdepth(150 750 mmat450 700nm; Fig.1.3)[36,102].ComparedwiththatofUV,light scatteringoccursweaklyinVislight.However,Vislightshowsstrongabsorbancebyyellow pigmentsaswellasmelaninand(oxy)hemoglobinmoleculesinitsshorterrange (400 600nm)(Fig.1.3)[33,104].Suchabsorptionisasourcefortheauto fluorescenceoften observedinimagingstudiesinvivo,whichreducesresolutioncapability[105].Vislight alsoshowsincreasedabsorptionbywaterinthelongerrangeofitswavelength( 600nm) [29].Forthisreason,Vislightisbettersuitedforimagingatissuesamplethanabloodsample, whichconsistsmostlyofwatermolecules[29,36].
Vislightservesasaprimaryexcitationsourcein fluorescentimagingstudiesofNPs labeledwithstandarddyemoleculessuchas fluoresceinisothiocyanate,AlexaFluor,rhodamine,andcyanine(Table1.1).LikeUVA,VislightofferssignificantutilityinPDTapplications.ManyphotoactiveNPsincludingnano-TiO2 [60 62],nano-ZnO[63],GOnanosheet [64,65],andfullerene[66,67]employVisirradiationforROSproduction.Vislightalsoplays anessentialroleinPTTapplicationsduetoitsstrongabsorptivitybynoblemetalNPssuchas nano-Auandnano-Ag(500 800nm)[5,6,46].
Initsapplicationsforcontrolleddrugdelivery,Vislightplaysalesssignificantrolethan thatoflong-wavelengthUVA.Currently,mostlinkermoleculesdevelopedforlight-triggered cleavagerequirephotonabsorptionwithhigherenergyequivalenttothatofUVAorUVB[7]. Onlyafewlinkerstructures,includingcyanine(690nm)[93,106]orcoumarin-basedlinkers (430nm)[92],offerlinkercleavageinresponsetostimulationbyVislight.Alternatively,the mechanismoftwo-photonexcitationisoccasionallyapplicableinVislight induceddrug release(Fig.1.5)[90].Thishasbeenreportedinanumberoftherapeuticagentsincluding chlorambucil[89]and4-hydroxytamoxifen[94].
1.3.3Nearinfraredlight
NIRlightcomprisesalongerrangeofwavelengthsspanningfrom700to2500nm (Fig.1.2).ItislessscatteredthanVislight.NIRlightislessabsorbedby(oxy,deoxy)
FIGURE1.3 (A)Molarabsorptivity(ε)ofmajorchromophoresinbloodincludingwater,hemoglobin(Hb)and oxygen-boundhemoglobin(HbO2).(B)Depthofskinpenetrationbyultraviolet(UV),visible(Vis),andnear-infrared (NIR)light.Note:Eachplotispreparedfromvaluesreportedinliteratureascitedbelow. W.S.Pegau,D.Gray,J.R.V. Zaneveld,Absorptionandattenuationofvisibleandnear-infraredlightinwater:dependenceontemperatureandsalinity,Appl. Opt.36(1997)6035 6046;F.E.Robles,S.Chowdhury,A.Wax,Assessinghemoglobinconcentrationusingspectroscopic opticalcoherencetomographyforfeasibilityoftissuediagnostics,Biomed.Opt.Express1(2010)310 317.
hemoglobins(39% 64%)andlipidsthanthatoccurringwithVislight(Fig.1.3)[105].Their absorptiongraduallydecreasesasthelightwavelengthincreases.Watermoleculescontribute tothemostsigni ficantabsorptioninthisregion.Overall,NIRlightshowsthehighesttissuepenetrationabilityamongallthreelightsources,reachingasdeepas1200 2200 mmat 800 1200nm[102].
AshortersegmentofNIR,whichextendsfromapproximately650to950nm,isreferredto asthe firstbiologicalwindow(I-BW)foropticalimaging[35,107].Relativetothelonger segment,thisNIRoffersgreatbene fitsforopticalimagingofNPsinvivo[34,35,105]because
ofitslowerabsorptionbywaterandhemoglobinmolecules[104].NIRsegmentslongerthan 950nmserveastwoadditionalwindowsforopticalimaging thesecondbiologicalwindow (II-BW;950 1350nm)andthirdbiologicalwindow(III-BW;1500 1800nm)[107].ThisNIR rangeshowsalowerleveloftissueauto fluorescencethanthatofI-BW[107],whichcan improvethesignal-to-background(noise)ratio.However,inthesespectralranges,bothwater andhemoglobinmoleculesincreasetheirabsorptivitybyapproximatelyonetotwoordersof magnitudeoverthatofI-BW[104].Suchhigherabsorptioncontributestoalocalheatingeffect,limitingthescopeoftheirutility.
NIRlightcarriesthelowestenergy,limitingitsapplicabilityinimagingandtherapeutic nanotechnology.ItsapplicationsarelimitedtoacertainclassofdyemoleculesorNPsthat showabsorptionincludingsingle-walledcarbonnanotubes(808nm)[54],metaloxideNPs [55 57],andupconversionnanocrystals(UCNs;808,980nm)[14,48 53].OftheseNPs, UCNspossessauniquemechanismofphotophysicalactivationinwhichNIRabsorption leadstoluminescenceemissionatashorterwavelengthintheUVAandVisregions [3,48,49].ThispropertyofupconversionluminescenceservesasausefulrouteforUCNdetectionandimagingthatisachievablewithoutlabelingwithanexternaldyemolecule(Table1.1) [14,40].Inaddition,itsluminescenceemissionallowsfortherapeuticapplicationsthatare otherwiseenabledbyactivationthroughonlyUVAorVislight.TheseincludeNIRinducedROSproductionforPDT[14,27,50,51,53,95,96]andlinkercleavageforcontrolled drugrelease[14,40,53,97,98].
Insummary,selectinganoptimallightsourceplaysacriticalroleintheimagingandtherapeuticapplicationsofmultifunctionalNPs.Itrequirescarefulconsiderationinthedesign phaseoftheseNPs.Avarietyofportablelamps,LEDdevices,andlaserequipmentare commerciallyavailableassummarizedin Table1.3.
TABLE1.3 Listofcommerciallightsources.
LightWavelength(nm)TypeSupplier
UVUVA254LightbulblampSpectroline
UVB312
UVA365LEDlampNichiaCorp.
Visible420LEDlampLuzchemResearch;NichiaCorp.
445 465(blue)
510 530(green)
580 600(amber/yellow)
630 650(red)
Near-infrared808PortablelaserCNIOptoelectronics;ThorLabs
1.4Nanotechnologyforphototherapy:overview
1.4Nanotechnologyforphototherapy:overview
NPsdesignedforphotoapplicationsarebroadlydividableintotwogroupsaccordingto theirintrinsiccoreproperties:(1)anNPconstructmadeofaphotoactivecoreand(2)an NPconstructthatlacksaphotoactivecorebutpresentsaperipheralphotoactivemolecule eitherattachedthroughcovalentconjugationornoncovalentlyencapsulatedinashelllayer orporouscorestructure.ThoseNPsthatbelongtothe firstgroupvarywidelyinthesize, shape,andcompositionofthecoreelementsthatconferintrinsicphotoactivity.Theseinclude nanogoldornanosilverintheshapeofananosphere[5],nanorod[5],ornanocage[1]aswell asTiO2 nanosphere[4,5],carbonnanotube[6],graphenenanosheet[3],andhexagonaldiskshapedUCN[2,3](Fig.1.4).
EachNPthatbelongstothesecondgrouphasamodificationinthecoreorperipherythat allowstheinductionoflight-controlledactivity.ModificationoftheseNPsinvolvesdrug
FIGURE1.4 Divisionofnanometer-sizedparticles(NPs)(size1 1000nm)byintrinsicphotoproperty. MSN, mesoporoussilicananoparticle; QD,quantumdot; UCN,upconversionnanocrystal. S.K.Choi,Mechanisticbasisoflight inducedcytotoxicityofphotoactivenanomaterials,NanoImpact3 4(2016)81 89.Copyright © 2016Elsevier.
conjugationthroughaphotocleavablelinkerforlight-controlledrelease[7].Italsoinvolves photosensitizerattachmentorencapsulationforPDTinwhichthephotosensitizermolecule intheNPconstructcatalyzestheproductionofROSuponstimulationbylight[108,109]. Regardlessoftheirclassi fication,thesephotoactivenanomaterialsaredesignedtooffer certaintherapeuticmodalitiesbasedondrugrelease,PTT,andPDT.
1.4.1Light-controlleddrugrelease
Useoflightprovidesanactivemechanismtoenablethereleaseofapayloadlinkedtoa nanoscalecarrier[7,110].Thisisachievableusingaclassofaromaticlinkermoleculesthat displayphotocleavableproperties.Eachlinkerhastwofunctionalarmsdesignedinan orthogonalmanner.Thus,itsphotocleavablefunctionalityservesfortetheringapayload, whileitssecondfunctionalityservesforNPconjugation,whichremainsasastablelinkage (Fig.1.5).Thephotocleavablelinkerengagesinpayloadreleasebyitslightabsorption,which occursviatwomechanisms,one-photon(single-photon)andtwo-photonabsorption.
Mostreleasedstudiesreportinginvitroandinvivoresultsinvolvelinkercleavage conferredbytheone-photonmechanism[7,110 113].Thismechanismisbroadlyapplicable toexistingphotocleavablelinkers[114]including ortho-nitrobenzene[72,110,115 117],thioacetal ortho-nitrobenzene[87],coumarin[90,115,117],carbazole[118,119],quinolone[120],xanthene[121], ortho-hydroxycinnamate[122],benzoin[123,124],andbenzophenone[125].The efficiencyofdrugreleaseisdeterminedbythequantumef ficiency(F)oflinkercleavage, whichisdefinedasthenumberofmoleculescleavedperthenumberofphotonsabsorbed. Releaseefficiencyvarieswidelywithvariousfactors,butitlargelydependsonlinkertypes andactivationwavelengths[87,94,118,126,127].
UsingUVAorUVBlightishighlyeffectiveforone-photonactivationinmostlinkers.In contrast,Vislightthatcarrieslowerenergyshowsrelativelylowquantumefficiencyfor linkercleavagebyone-photonactivation.Onlyafewlinkersretaintheabilitytoundergoa cleavageuponstimulationbyVislight.Theseincludethosederivedfromcoumarin (420nm)[89,90,92,113,126,127]andquinoline(458nm)[128].Ofparticularnoteisa cyanine-basedlinkerthatdisplaystheabilityforefficientcleavagebyVis(690nm)orNIR light(780nm)[93,106].Itsmechanismoflinkercleavage,however,isattributabletoitschemicalreactionwithsingletoxygenspecies(ROS)producedbylightstimulationratherthanits photochemicalfragmentation(Fig.1.5).
NIRlightdoesnotcarryenoughenergytoallowforone-photonabsorptionbymostlinker molecules.Instead,NIRisapplicableforlinkercleavageviatwo-photonabsorption,whichis equivalenttoaUVAenergylevel.Linkerssuchas ortho-nitrobenzeneandcoumarinshowthe abilityforcleavagebyactivationat800nm(Fig.1.5)[89,94].However,linkercleavageby two-photonabsorptionislesseffectivethanthatofone-photonabsorption,anditleadsto alowerquantumefficiencyindrugrelease[94].
1.4.2Photothermaltherapy
LightstimulationcanproducelocalizedheatincertaintypesofNPsorpolymersviathe mechanismofplasmonicactivation(Fig.1.6)[5,25,47,129 131].Thisphotothermalactivation occursefficientlybynoblemetalNPssuchasnano-Au[5,6,91]andnano-Ag[46]bylight
FIGURE1.5 (A)Conceptforlight-controlleddrugdeliveryinnanotechnology.(B)Underlyingmechanismsof lightabsorptionbyphotocleavablelinkers:one-photon(upper)andtwo-photon(lower). NP,nanoparticle.
absorptionintherangeofVisandNIRlight(500 800nm).Theproducedheatundergoes rapiddissipationintheareaaroundtheNP,offeringamechanismforelevatinglocaltemperaturethatishighenoughtoinducealethaleffectinpathogensandcancercellsinclose proximity[132,133].ThisphotothermaleffectservesasamechanisticbasisforPTT[129,132].
(A)
(B)
FIGURE1.6 (A)PlasmonicphotothermalactivationofAunanorodsand(B)itsapplicationforphotothermal therapy. AuNP,goldnanoparticle. S.K.Choi,Mechanisticbasisoflightinducedcytotoxicityofphotoactivenanomaterials, NanoImpact3 4(2016)81 89.Copyright © 2016Elsevier.
Thistherapeuticmodalityoffersapromisin gopportunityinthetrea tmentofcancersand antibacterialinfections[27 ,53].
Theefficiencyofphotothermalheatingbymetalnanomaterialsvarieswithcorecompositionandstructuralpropertiesincludingsize[133],shape[133 135],andsurfacemorphology [134,136,137].Inparticular,theaspectratio(width length 1)thatdefinestheNPshape playsthemostcriticalroleindeterminingphotothermalefficiency.Thisphotothermalheatingoccursmoreef ficientlyathigheraspectratios,anditsextentispositivelycorrelatedwith theinductionofcytotoxicity[5,138].NonsphericalAunanorodshavinganaspectratio greaterthan1caninducecytotoxicitymoreeffectivelythanthatinducedbyAunanospheres havinganaspectratioof1[133,139,140].
Tumor cell
Cell death
AuNP
(A)
(B)
1.4.3Photodynamictherapy
Asanothertherapeuticmodality,lightstimulationenablesphotoactivenanomaterialsto produceROS[141].Itbelongstoaclassofchemicallyreactivemoleculesthatconsistsof variousspeciesincludingfreeradicals( OH, OOH, NO),superoxideanion( O2 ),orsinglet oxygen(1O2)species[142](Fig.1.7).
ROSproductionoccursthroughlightactivationofeitheraphotoactivecoreorseparately throughsmallphotosensitizermoleculesencapsulatedinsideorattachedtoNPs[141].
FIGURE1.7 (A)Mechanisticbasisofphotodynamictherapy.Light-inducedproductionofreactiveoxygenspecies(ROS)asillustratedwithaphotoactivenanocore(top)andperipherallyattachedphotosensitizermolecules (bottom).(B)ROS-mediatedcellulardamageleadingtocelldeath. S.K.Choi,Mechanisticbasisoflightinducedcytotoxicityofphotoactivenanomaterials,NanoImpact3 4(2016)81 89.Copyright © 2016Elsevier.
AnumberofphotoactivecoreshaveaprovenabilityfordirectROSproductionincluding carbonnanotubes(single-walledandmultiwallednanotubes)[6 ,143, 144 ],fullerene(C 60 ) [66 ,67],GOnanosheet[ 64 ,65 ],nano-TiO2 [4 ,60 62, 145 ]andnano-ZnO[ 63 , 146],andQDs [41 ,147 ].CoreactivationoccursbyirradiationintheUV Visrange(360 600nm).Photosensitizermoleculesarealsoabletoproducesingletoxygen( 1O 2)speciesbyUV Vis irradiation[148].
1.5Summary
Photoactivenanomaterialshavemadeasignificantcontributionintheapplicationofnanotechnologyforphototherapy[7,12 14],imaging[15,16],anddiagnosis[17].Asacontrol, lightirradiationplaysacommonroleindefiningandcharacterizingtheirphotophysical andphotochemicalproperties.LightsourcesforapplicationconsistofUV,Vis,andNIRlight, eachdisplayingadistinctsetofpropertiesinabsorption,scattering,andtissuepenetration.
UsingUVlighthascertaindrawbacksandispartlylimitedbyitsscatteringandsuboptimaldepthofpenetration.However,longUVAoffersoutstandingbene fitsduetoitslackof intrinsiccytotoxicityanditstunableenergy,whichisapplicableforQDimaging,ROSproduction,orenablingalinkercleavageforcontrolleddrugdelivery[7].Vislightalsoplays animportantroleinNPdetection,imaging,anddrugrelease.ItsuseismoreevidentintherapeuticapplicationsforPTTandPDTperformedwithnoblemetalNPs,nano-TiO2,GO,or photosensitizer-conjugatedNPs[22 24].NIRlightoffersbene ficialpropertiessuchaslow lightscatteringwithanabilityfordeeptissuepenetration.Itplaysanessentialroleinimaging applicationsinvivoattheI-BWorII-BW[53].NIRlackssuf ficientenergytoinduceeither photochemicallinkercleavagefordrugdeliveryorNPactivationforPDTorPTT.However, UCNsallowNIR-inducedtherapeuticeffectsviadrugrelease,ROSproduction,photothermal activation,ortheircombination.
Insummary,identifyingtherightlightsourcesishighlycriticalfordesigningandconductinglight-controlledNPsystemsforimaging,drugdelivery,PTT,andPDTassummarizedin Table1.2.Thischapteraimstohelpunderstandthebasicpropertiesoflightfor theoptimaldesignofphotoactivenanomaterials,imagingmethods,andtherapeuticapplications.Detaileddescriptionsoftheseconstitutethesubjectsoftheindividualchaptersthat follow.
Abbreviations
AuNP Goldnanoparticle
CDs Carbondots
CNTs Carbonnanotubes
GO Grapheneoxide
GQD Graphenequantumdot
Hb Hemoglobin
HbO2 Oxygen-boundhemoglobin
I-BW (First)biologicalwindow
II-BW (Second)biologicalwindow
III-BW (Third)biologicalwindow
NIR Near-infrared
NPs Nanometer-sizedparticles
PDT Photodynamictherapy
PTT Photothermaltherapy
QDs Quantumdots
ROS Reactiveoxygenspecies
SWNT Single-walledcarbonnanotube
UCN Upconversionnanocrystal
UV Ultraviolet
UVA Long-wavelengthUV
UVB Medium-wavelengthUV
UVC Short-wavelengthUV
Vis Visible
F Quantumefficiency
Acknowledgments
TheauthorwishestothankfundingsupportovertheyearsbyGlobalInnovationInitiativefromtheBritishCouncil andtheUSDepartmentofState.
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