Communicationpubs.acs.org/JACSSite-Speci?cSurfaceFunctionalizationofGoldNanorodsUsingDNAOrigamiClamps
ChenqiShen,?Xiang*,Lan,??XuxingLu,?TravisA.Meyer,?WeihaiNi,?YonggangKe,*,?andQiangbinWang?KeyLaboratoryofNano-BioInterface,DivisionofNanobiomedicineandi-Lab,SuzhouInstituteofNano-TechandNano-Bionics,ChineseAcademyofSciences,Suzhou215123,China?WallaceH.CoulterDepartmentofBiomedicalEngineering,GeorgiaTechandEmoryUniversity,EmorySchoolofMedicine,Atlanta,Georgia30322,UnitedStates
*
SSupportingInformationABSTRACT:PrecisecontroloversurfacefunctionalitiesForinstance,Mirkinandco-workers12fabricatedgoldnano-ofnanomaterialso?ersgreatopportunitiesforfabricatingparticles(AuNPs)asymmetricallysurface-functionalizedwithcomplexfunctionalnanoarchitecturesbutstillremainsbothnormalandextendedoligonucleotideswiththeassistancechallenging.Inthiswork,wesuccessfullydevelopedaofmagneticmicroparticles,andtheseanisotropicparticleswerenovelstrategytomodifyagoldnanorod(AuNR)withfurtherusedasbuildingblocksfortheconstructionofuniquespeci?csurfacerecognitionsitesusingaDNAorigamiheterostructures.WiththeadvancementofDNAnano-clamp.AuNRswereencapsulatedbytheDNAorigamitechnology,self-assembledDNAorigamihasproventobeathroughhybridizationofsingle-strandedDNAontheversatileplatformforconstructingfullyaddressable,arbitrary-AuNRsandcomplementarycapturestrandsinsidetheshapednanostructures.13Noble-metalnanoparticles,14quan-clamp.Anothersetofcapturestrandsontheoutsideofthetumdots,15clampcreatethespeci?crecognitionsitesontheAuNRdocked?uorescenttospeciprobes,16andbiomolecules17havebeenprecisely?clocationsonDNAorigamisca?oldssurface.Bymeansofthisstrategy,AuNRsweresite-tofabricateavarietyofwell-orderednanoarchitectures.speci?callymodi?edwithgoldnanoparticlesatthetop,Therefore,theuseofDNAorigamicouldbeapromisingmiddle,andbottomofthesurface,respectively,totechniquetorealizesingle-sitesurfacemodi?cationofnano-constructaseriesofwell-de?nedheterostructureswithparticles,whichhasnotbeenreportedbefore.
controlled“chemicalvalence”.OurstudygreatlyexpandsInthiswork,wedevelopedanovelstrategytorenderagoldtheutilityofDNAorigamiasatoolforbuildingcomplexnanorod(AuNR)withspeci?csurfacerecognitionsitesusingananoarchitecturesandrepresentsanewapproachforDNAorigaminanostructure.AnopenDNAorigaminano-precisetailoringofnanomaterialsurfaces.structure,termeda“DNAclamp”,wasdesignedwithcapturestrandsontheinsidefaces,causingtheDNAclamptoclosearoundtheAuNRafterhybridizationwiththecomplementarySurfacefunctionalitiesofnanomaterialsplayaparticularlyDNAstrandsontheAuNRsurface,fullyencapsulatingthedecisiveroleinregulatingtheirphysicalandchemicalnanorodsurface.TheDNA-clamp-coveredAuNRpossessesaproperties,suchasbiocompatibility1andcatalyticactivity,2fullyaddressablesurface,o?eringunprecedentedsite-speci?cbecauseoftheirhighsurface-to-volumeratios.Therefore,functionalityandpromisingmorepreciseconstructionofmethodsforsurfacemodi?cationofnanoparticleshavebeencomplexnanostructures.Furthermore,thisnewapproachinvestigatedindepth.Classicsurfacemodi?cationprocessesexpandstheusageofDNAorigamifromaddressableassemblyisotropicallydecoratethewholenanoparticlesurface,thusoffunctionalcomponentstosite-speci?csurfacemodi?cationcreatingasingletypeofsurfacefunctionality.3Inrecentyears,ofnanomaterials,enablingtherationaldesignandprecisemoree?ortshavebeendedicatedtofabricatingsurface-fabricationoffunctionalnanomaterialsandnanostructures.anisotropicFigure1schematicallyillustratesthestep-by-stepprocessfor4nanoparticlesdisplayingmultiplesurfacefunction-alitiesbyutilizingmethodssuchasdeposition,5lithography,6surfacefunctionalizationoftheAuNR.First,aDNAclamptemplating,7etc.Nonetheless,theseanisotropicfunctionaliza-consistingoftwohalf-tubeswithequallengthsof56nmlinkedtionmethodsstilllacktheprecisionneededtomanufacturebytwo?exiblehingeswasdesigned.Atotalof16capturefunctionalnanomaterialswithcustom-designedindividualstrandswerearrangedinthreestripesprotrudingfromtherecognitionsites.AnewstrategythatcangeneratenanomaterialinsidefacesoftheDNAclamp.A13nm×38nmAuNRsurfaceswitharbitrarysingle-sitemodi?cationscouldfacilitatefunctionalizedwiththiolatedsingle-strandedDNA(ssDNA)theconstructionofnewnanomaterialswithgreatercomplexitywasmixedwiththeself-assembledDNAclamp,leadingtoandpotentiallynewfunctionalities.
hybridizationofssDNAontheAuNRsurfacewiththeDNAhasemergedasapowerfulmoleculeforsurface-complementarycapturestrandsinsidetheclamp.This
anisotropicfunctionalization8becauseofitsoutstandingfeaturesincludingsequenceprogrammability,9distinctiveReceived:November4,2015molecularrecognition,10andfacilechemicalmodi?cations.11Published:January29,2016
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JournaloftheAmericanChemicalSocietyCommunicationFigureaAuNR.1.(a)SchemeTheAuNRshowingwasthe?rstprocessmodi?foredsurfacewiththiolatedfunctionalizationssDNA.TheofssDNA-functionalizedclamphybridization(withwithasizeAuNRwasthenencapsulatedbytheDNAtheofcapture26nmstrands×28insidenmtheinsolution)clamp.(b)throughThreegroupsrecognitionofcapturesitesonstrandstheAuNRoutsidesurfacetheafterclampfunctionalizationformedthreespecibythe?cDNAtheclamp.AtotestadditionthesiteofAuNPscollectionselectivitymodiofof?theedheteroassemblieswithwasthencreatedwithAuNR.
di?erentcomplementaryssDNAFigure2.CharacterizationoftheDNAclampandthefunctionalizedAuNRs.hybridizationdrivestheDNAclamptocloseandencapsulateoftheAuNR,formingahexagonalcrosssectionwithamaximumssDNA-moditheAuNRs(a)Daylight-?edandandAuNRs.their(b)LaneheteroassembliesUV-light-illuminatedagarosegelimages2:site-selectivewithDNA-clamp-coveredAuNPs.Lane1:lengthandwidthof28and26nm(Figure1a).TodemonstrateAuNRs.thesiteselectivityoftheDNA-clamp-modi?edAuNR,we(topsite),Lanestwo3(top?5:AuNRandbottom?AuNPsites),heteroassembliesorthree(top,containingmiddle,oneandintroducedthreegroupsofuniquecapturestrandsprotrudingbottomfromtheoutersurfaceoftheDNAclamp,asshowninFiguretarget1b.ThefunctionalizedAuNRthuspossessedthreespeci?cNegative-stainedproductssites)6innmTEMlanesAuNPs.2images?5areLanehighlighted6:theDNAof(c)DNAbytheorigamiclampsyellowclamp.Theandboxes.(d)(c,site-d)recognitionsites,locatedatthetop,middle,andbottomoftheselectiveAuNRs.
AuNRsurface.WethenaddedAuNPsfunctionalizedwithcorrespondingcomplementaryDNAsequencestobuildaseriesAuNRwasahalo,thethicknessofwhichwasvisibleas～2nmofAuNR?AuNPheteroassemblieswithprecisespatialintheTEMimages(Figure3a).
con?gurations.
Toverifyourstrategyforsite-speci?cfunctionalizationoftheThessDNA-modi?edAuNRs,DNA-clamp-coveredAuNRs,AuNRs,AuNPsconjugatedwithssDNAsequencescomple-andAuNR?AuNPheteroassembliesweresubsequentlyana-mentarytothethreegroupsofcapturestrandsontheouterlyzedbyagarosegelelectrophoresis.TheresultinggelimagessurfaceoftheDNAclampwereaddedtoconstructasetofunderdaylightandUVlightareshowninFigure2a,b,well-de?nedAuNR?AuNPheterostructures.Itshouldbenotedrespectively.Lane1correspondstothessDNA-modi?edthatbecauseofthe?exibilityoftheDNAdoublehelix,theAuNRs,whilelane2containsAuNRscoveredbytheDNApositionoftheAuNPsdockedontheAuNRsurfacemightshiftclamp.Thedecreasedmobilityofthetargetbandinlane2isunderTEMmeasurement.Takingthispointintoaccount,wepresumablyduetotheextraresistanceaddedbytheDNApredictedthatthemaximumdistancefromthesite-speci?callyclamp.Lanes3?5representthesite-selectiveAuNRsassembleddockedAuNPstotheDNAclampcoveringtheAuNRsurfacewithone(topsite),two(topandbottomsites),andthree(top,wouldbe7.5nm(Figure3a),consideringthatthecapturemiddle,andbottomsites)6nm-sizedAuNPs,respectively.AstrandsontheoutersurfaceoftheDNAclampwere22baseslightdecreaseinthemobilityofeachassemblywasobservedpairslong.Therefore,allofthesampleswithdistancesbetweenwithsuccessiveadditionsofAuNPs.Lane6correspondstothetheAuNPandDNAclampsmallerthan7.5nmwereDNAclampasareference,whichpossessedsimilarmobilityasconsideredtheproductsthatwerehybridizedthroughourtheDNA-clamp-coveredAuNR.
site-speci?cfunctionalizationstrategy.
Theself-assembledDNAclampandthesite-selectiveDNA-At?rst,asingleAuNPwasintroducedateithertopormiddleclamp-coveredAuNRswerecon?rmedbytransmissionelectronsiteoftheAuNRtoverifythesite-selectivefunctionalizationmicroscopy(TEM)afterpuri?cation,asshowninFigure2c,d.strategy.AspresentedinFigure3b,c,theTEMimagesclearlyThenegative-stainedtwo-dimensionalTEMimagesoftheopenillustratethatmostoftheAuNRshada6nm-sizedAuNPDNAclampshowedthatitpossessedtwohalf-tubesconnectedselectivelyattachedatthetopormiddlesite,respectively.Theby?exiblehinges.Eachhalf-tubeexhibitedaquasi-rectangularstatisticalanalysisindicatedthatupto84%or90%ofthemorphologymatchingourdesign.Thelengthofeachhalf-tubeproducts,respectively,possesseddistancesfromtheAuNPtowasapproximately50nm,whichisconsistentwithourdesigntheDNAclampshorterthan7.5nm,whichveri?esthehighandsimilartothelengthoftheAuNRs.Hybridizationbetweene?ciencyofourstrategyinpreciselyconstructingAuNRswiththessDNAontheAuNRsurfaceandthecomplementarysite-selectivefunctionality.ThesmallpopulationwithdistancescapturestrandsinsidetheDNAclampledtoa?nalcore?shelllongerthan7.5nmwaspossiblyattributabletoincompletenanoarchitecturewiththeDNAclampcoveringtheAuNRwithhybridizationoftheAuNPandtheDNAclampontheAuNRathicknessof2nminthedriedstate.BecauseofitslowersurfaceorlooseencapsulationoftheAuNRbytheDNAclamp.contrastinTEMmeasurements,theDNAclamparoundthe
Inanothersetofexperiments,alarger8.5nm-sizedAuNPwas
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JournaloftheAmericanChemicalSocietyCommunicationFigure4.TEMimagesanddistancedistributionsoftheassembliesofAuNRsbottomwithsitesoftwotheAuNPs:AuNR;(a)(b)twotwo66nm-sizednm-sizedAuNPsAuNPsatatthethetoptopandandmiddlesizedsitesoftheAuNR;(c)one6nm-sizedsizedAuNPAuNPatatthethetoptopandsiteandbottomonesites8.5nm-sizedoftheAuNPAuNR;andAuNP(d)oneattheone8.5middle6nm-nm-Figuresite(a)Schematic3.Site-specimodel?coffunctionalizationthemaximumdistanceofAuNRsbetweenwithathesingleAuNPAuNP.andnm-sizedoftheAuNPAuNR;at(e)theonemiddle8.5nm-sizedsiteoftheAuNPAuNR.attheRed,topgreen,siteandandoneblue6thecolorsnm-sizedDNAAuNPclamp.site-selectively(b,c)TEMimagesanchoredand(b)distanceatthedistributionstop(red)orof(c)aat6respectively.representthe25nm.
Thebondsscalebarsformedintheatzoomed-inthetop,middle,TEMimagesandbottom(insets)sites,aredistributionsmiddle(green)ofaAuNR.(d,thetop(red)oforan(e)8.5atnm-sizedthemiddleAuNPe)(green)site-selectivelyTEMimagesofaAuNR.anchoredanddistanceThecolored(d)atTheTEMimagesinFigure5showthattheAuNPswerecolumnsdockedatthetop,middle,andbottomsitesoftheAuNR,fullyAuNR?AuNPintheheterostructureshistogramsrepresentwithdistancesthepopulationsshorterofthanthe7.5formednm,con?rmingtheprecisesiteselectivityoftheAuNRsurface.
whileassembliesthedashedzoomed-inTEMwithcolumnsdistancesrepresentthepopulationsofthedislocatedimages(insets)largerarethan257.5nm.
nm.ThescalebarsinselectivelyassembledontheAuNRsurface.Similartoexperimentswiththe6nm-sizedAuNPs,weobservedthatmostoftheAuNPswerelocatedatthetop(78%)ormiddle(76%)siteoftheAuNRatadistancebetweentheAuNPandtheDNAclampshorterthan7.5nm,asshowninFigure3d,e.ThisslightlydecreasedyieldwasattributedtosterichindranceFigureduetotheincreasedsizeoftheAuNPs.
threeNext,theproposedsite-selectivefunctionalizationstrategyAuNR;65.TEMimagesofassembliesofAuNRswiththreeAuNPs:(a)(b)nm-sizedone8.5AuNPsnm-sizedattheAuNPtop,atmiddle,thetopandsitebottomandtwosites6nm-sizedofthewasfurtherprovedbyintroducingtwoAuNPsatspeci?csitesAuNPsofaAuNRtoassemblecomplexnanostructures.Figure4sizedexhibitsacollectionofTEMimagesanddistancedistributionsandbottomAuNPatthesitesatmiddletheandbottomsitesoftheAuNR;(c)one8.5nm-ofmiddletheAuNR.siteandThetwoscale6barsnm-sizedintheAuNPszoomed-inattheTEMtopoftheseassembliesfollowinghybridizationof6nm-and8.5images(insets)are25nm.
nm-sizedAuNPsattwoofthethreesitesofaAuNR.TheTEMimagesshowthatthetwodi?erent-sizedAuNPsweresite-Insummary,wehavesuccessfullydemonstratedprecisespeci?callylocatedontheAuNRsurfacethroughthecontroloftheAuNR’ssurfacefunctionality,includinghybridizationofssDNAontheAuNPs.
modulationofitschemicalvalencefrommonovalenttoFinally,threeAuNPswerehybridizedwiththeDNAclampdivalentandtrivalentaswellasthesite-speci?cfunctionalitytoachievemorecomplexAuNR?AuNPheterostructuresinfromthetoptothemiddleandbottomoftheAuNR,bytakingwhichthelocalizationoftheAuNPsontheAuNRsurfacewasadvantageofDNAnanotechnology.ADNAclampwaspreciselycontrolledbythesiteselectivityoftheDNAclamp.
employedtoencapsulatetheAuNRandformtheAuNR@
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JournaloftheAmericanChemicalSocietyCommunicationDNAclampcore@shellstructure,inwhichtheDNAclampZ.;Han,B.;Gao,Y.;Tang,Z.Nanoscale2014,6,4498.(d)Xu,L.;endowedtheAuNRwithcontrolledchemicalvalenceandsite-Kuang,2012,134H.;,1699.Xu,C.;(e)Ma,Jones,W.;M.Wang,speci?cfunctionalityafterrationaldesignofthesequenceandR.;Seeman,L.;Kotov,N.C.;N.A.Mirkin,J.Am.C.Chem.A.ScienceSoc.locationofthecapturestrandsprotrudingfromtheDNA2015,347,1260901.
clamp.AuNPsconjugatedwithDNAsequencescomplemen-tarytotheprotrudingsequenceontheDNAclampwereXing,(9)Song,H.;Wang,T.;Tang,Z.;Li,L.;J.;Tan,Liang,L.H.;H.;Wang,Lu,Y.X.;Angew.Satyavolu,Chem.,N.Int.S.Ed.R.;hybridizedwiththeAuNR,anddi?erentpatternsofAuNR?2015AuNPheterostructureswereassembledinhighyield,(10),54Wang,,8114.
Q.;Yang,X.;Wang,K.;Tan,W.;Gou,J.Analyst2008,demonstratingthesuccessofoursite-selectiveAuNR133functionalizationstrategy.OurstrategyrepresentsanewS.(11),1274.
J.Am.Hardisty,Chem.R.Soc.E.;2015Kawasaki,,137,F.;9270.
Sahakyan,A.B.;Balasubramanian,approachforpreciselytailoringthenanoparticlesurface,andweexpecttorealizesite-speci?ctuningofsigni?cantopticalChem.(12)Xu,propertiessuchassurface-enhancedRamanspectroscopyand(13)Soc.X.;(a)2006Rosi,Iinuma,,128N.L.;Wang,Y.;Huo,F.;Mirkin,C.A.J.Am.R.;,9286.
Ke,Y.;Jungmann,R.;Schlichthaerle,T.;metal-enhanced?uorescencefromthesepreciselycontrolledWoehrstein,nanoarchitectures.Additionally,site-selectivecatalysismightbeNuckolls,C.;J.Wind,B.;Yin,S.J.P.Angew.ScienceChem.,2014,Int.344Ed.,65.2012(b),51Wang,,11325.R.;achieved,andasmartcascadecatalyticreactionsystemcouldbe(c)furtherdesignedsincewecanpreciselycontrolthespatialQ.;Yao,location2966.Wang,G.;(d)Zhou,L.;Li,Huang,J.;Chao,J.;Pei,H.;Liu,H.;Zhao,Y.;Shi,J.;Huang,C.;Duan,W.;Fan,X.;Liu,C.N.Angew.Nat.Chem.,Commun.Int.2015Ed.,20156,8102.,54,■ofthecatalyticsites.
ASSOCIATEDCONTENT
M.;(14)Ho(a)Kuzyk,Simmel,A.;Schreiber,F.C.;Govorov,R.;Fan,Z.;A.Pardatscher,O.;Liedl,T.G.;NatureRoller,2012E.-gele,A.;,*
483Y.;,311.(b)SSupportingInformationTheSupportingInformationisavailablefreeofchargeonthe4320.Liu,(d)Z.;Tian,Yu,Chen,G.;Z.;Y.;Wang,Jiang,Lan,W.;X.;T.;Liu,Mao,Wang,W.;C.Q.Xin,J.SmallAm.H.L.;Chem.2013,Li,H.;Soc.9,3567.Ke,2015(c)Y.;,Li,Shih,137,ACSPublicationswebsiteatDOI:10.1021/jacs.5b11566.
W.Experimentaldetails,moreTEMimages,UV?vis(15)M.;(a)Gang,Schreiber,O.Nat.R.;Nanotechnol.Do,J.;Roller,2015E.;,10Zhang,,637.
T.;SchuNickels,ller,V.J.;extinctionspectra,electromagnetic?eldsimulations,(b)P.C.;Feldmann,J.;Liedl,T.Nat.Nanotechnol.2014,9,74.schematicdescriptionoftheDNAclamp,andDNA(16)Samanta,Pal,S.;Dutta,A.;Deng,P.;Wang,Z.;Liu,H.;Y.Deng,NanoscaleZ.;Zou,2014S.;,6Yan,,4486.
H.;Liu,Y.J.■sequences(PDF)
Phys.(17)Chem.Jusuk,CI.;2013Vietz,,117C.;,Raab,12735.
M.;Dammeyer,T.;Tinnefeld,P.Sci.AUTHORINFORMATION
Rep.2015,5,14075.
Corresponding*Authors
*yonggang.ke@emory.eduqbwang2008@sinano.ac.cn
Notes
■Theauthorsdeclarenocompeting?nancialinterest.
ACKNOWLEDGMENTS
ThisworkwassupportedbygrantsfromtheChineseAcademyofSciences“StrategicPriorityResearchProgram”(XDA01030200)andtheNationalNaturalScienceFoundationofChina(21425103)toQ.W.andagrantfromtheBiomedicalEngineeringDepartmentStartupFundandaBilliandBernieMarcusResearchAwardtoY.K.T.A.M.wassupportedbyan■
NSFGraduateResearchFellowship(GrantDGE-1148903).
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