A General and Robust Strategy for the Synthesis

A general and robust strategy for the synthesis ofnearly monodisperse colloidal nanocrystalsXinchang Pang, Lei Zhao, Wei Han, Xukai Xin and Zhiqun Lin*Colloidal nanocrystals exhibit a wide range of size- and shape-dependent properties andhavefoundapplicationinmyriadelds, incudingoptics, electronics, mechanics, drugdeliveryandcatalysis, tonamebutafew13. Syntheticprotocolsthatenable the simple and convenient production of colloidal nano-crystals with controlled size, shape and composition are there-foreof keygeneral importance4,5. Current strategiesincludeorganic solution-phase synthesis6, thermolysis of organometal-licprecursors4,7, solgel processes5, hydrothermal reactions8andbiomimeticanddendrimertemplating911.Often, however,these procedures require stringent experimental conditions,are difcult to generalize, or necessitate tedious multistepreactionsandpurication. Recently, linearamphiphilicblockco-polymer micelles have been used as templates to synthesizefunctionalnanocrystals12,13,butthethermodynamicinstabilityofthesemicelleslimitsthescopeofthisapproach. Here, wereportageneral strategyforcraftingalargevarietyoffunc-tional nanocrystals with precisely controlled dimensions, com-positions and architectures by using star-like block co-polymers as nanoreactors. This newclass of co-polymersforms unimolecular micelles that are structurally stable, there-fore overcoming the intrinsic instability of linear blockco-polymer micelles. Our approach enables the facile synthesisof organic solvent- and water-soluble nearly monodispersenanocrystals with desired composition and architecture, includ-ing coreshell and hollow nanostructures. We demonstrate thegenerality of our approach by describing, as examples, the syn-thesis of various sizes and architectures of metallic, ferroelec-tric, magnetic, semiconductor and luminescent colloidalnanocrystals.Owingtotheir abilitytodirect the aggregationof inorganicmaterials in well-dened, conned volumes, micelles of linearamphiphilic block co-polymers offer an attractive means by whichtosynthesizecolloidal nanocrystals, asrecentlyexploitedincon-junctionwithsolgel chemistry14. However, conventional linearpolymericmicellesarethermodynamicaggregatesof amphiphilicmoleculesabovetheircritical micelleconcentration1416. Theyarethereforedynamically stable, sotheircharacteristicsforagivensystem depend heavily on temperature and solvent properties, andthe shape of the micelles may change when experimental conditions,suchasconcentration, solvent, temperatureandpH17, arevaried.Only the nanoparticles that do not requirehigh-temperaturecon-versionfromprecursorscanbepreparedinsolutionbyreducingthe precursor entrapped within the block co-polymer micelles14.In contrast, our method is based on a series of multi-arm star-like block co-polymers comprising either all hydrophilic or hydro-philic/hydrophobic blocks that are covalently linkedtoa smallcore. These co-polymers form thermodynamically stable unimole-cular micelles (micelles composedof a single co-polymer), thesizeandshapeofwhichcanbetunedbychemicalsynthesis, andact as nanoreactors for the synthesis of inorganic materials17,18.Thestar-likeblockco-polymersusedherearepoly(acrylicacid)-block-polystyrene (PAA-b-PS) and poly(acrylic acid)-block-poly(ethylene oxide) (PAA-b-PEO) diblock co-polymers, andpoly(4-vinylpyridine)-block-poly(tert-butyl acrylate)-block-poly-styrene (P4VP-b-PtBA-b-PS), poly(4-vinylpyridine)-block-poly(tert-butyl acrylate)-block-poly(ethyleneoxide) (P4VP-b-PtBA-b-PEO), polystyrene-block-poly(acrylicacid)-block-polystyrene(PS-b-PAA-b-PS) andpolystyrene-block-poly(acrylicacid)-block-poly(ethylene oxide) (PS-b-PAA-b-PEO) triblock co-polymers. Werst synthesized plainnanoparticles using amphiphilic star-likePAA-b-PSdiblockco-polymeras atemplatetodemonstratetheeffectiveness of our strategy for producing a wide spectrumofhigh-quality nanoparticles (Fig. 1a, Supplementary Table S1,SectionSI). TheinnerPAAblockintheunimolecularmicellesishydrophilic and imparts the preferential incorporation of precursorsintotheinterior spaceoccupiedby21PAAblocks viaastrongcoordination bonding between the metal moiety of the precursorsandthefunctionalgroupsofPAA(COOH)19. Itisimportanttonotethat therewasnosuchcoordinationwiththeouterhydro-phobic PS blocks. Subsequent hydrolysis and condensation ofappropriate precursors in the mixed solvents of dimethylformamide(DMF)andbenzylalcoholformedthedesirednanoparticleswiththePAAblocks encapsulatedinside(seeSupplementarySectionSIII for the proposed formation mechanisms), while the surface ofthe nanoparticles was intimately and permanently connected withhydrophobic PS blocks (Fig. 1a).The synthesis of ferroelectric PbTiO3 nanoparticles with differ-ent diameters (Fig. 2a) was used as an example to illustrate the pro-tocol depicted in Fig. 1a. Representative high-resolutiontransmissionelectronmicroscopy (HRTEM) characterizationof9.8+0.4 nm PbTiO3 nanoparticles demonstrated that they had con-tinuouscrystallinelattices(Fig. 2a, lowerleft). Theformationofsingle crystals may be qualitatively understoodas follows. Thevolumefractionof PAAblocksencapsulatedinthe9.8+0.4 nmnanoparticle was only 13.8%, based on thermogravimetric analysis(TGA) measurements (SupplementarySectionSIV). Becausethereactiontemperaturewaslowerthanthedegradationtemperatureof the polymer templates (Td210 8Caccording toTGA), thechainsegments of the PAA-b-PS(for example, AAunits) mayeither substitute the atoms on a specic crystalline lattice of nano-particles and become part of the lattice structure or may intercalatethe lattices, thereby resulting insingle crystalline nanoparticles,regardless of the presence of PAAchains. Similar phenomenahavebeenbroadly observed in organicmolecule/inorganic crystalsystems2022. This will be the subject of future studies.Intriguingly, the volume ratio of DMF to benzyl alcohol in themixed solvents had a profound inuence on the shape uniformityof theresultingnanoparticles. Indeed, tailoringthesolubilityofpolymer chains usingmixedselective solvents canfacilitate theencapsulation of inorganic precursors. This led to a better denedspherical spacecomposedofinnerhydrophilicPAAblocks, fromSchool of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. *e-mail: [email protected] ONLINE: 2 JUNE 2013 | DOI: 10.1038/NNANO.2013.85NATURE NANOTECHNOLOGY | VOL 8 | JUNE 2013 | www.nature.com/naturenanotechnology 426 2013 Macmillan Publishers Limited.All rights reserved. Hydrolysis 21-arm star-likePAA-b-PS= -CD = -CD = -CD PAAprecursors-CD21Br--CD initiator 21Br--CD initiator ATRP of tBA PtBA ATRP of St PS PS PrecursorsPS Nano-particlesaAddingReaction ATRP of tBA P4VP ATRP of St PS Hydrolysis 21-arm star-likeP4VP-b-PtBAATRP of 4VP PtBA ShellCoreCorenano-particles21-arm star-likeP4VP-b-PtBA-b-PS(i) Adding shellprecursorsb(i) Adding core precursors(ii) Reaction (ii) ReactionPS PAA ATRP of tBA PS ATRP of St PS Hydrolysis Precursors21-arm star-likePS-b-PtBAATRP of St PtBA Hydrolysis PrecursorsPAA 21-arm star-like PS-b- PAA-b-PSPS Nano-particlescAdding Reaction HollowOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOPMBPMBPMBPMBPMBBMPBMPBMPBMPBMPBMPBMPBMPBMPOBMPBMPBMPPMBPMBPMBBMP21Br--CD initiator OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOPMBPMBPMBPMBPMBBMPBMPBMPBMPBMPBMPBMPBMPBMPOBMPBMPBMPPMBPMBPMBBMPOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOPMBPMBPMBPMBPMBBMPBMPBMPBMPBMPBMPBMPBMPBMPOBMPBMPBMPPMBPMBPMBBMPBrOBrOHOHOOHOOOHHOOHOOHOHOOHOOHOOHOHOOOHOHHOOOOHOHHOOOOHOHHOOCorenano-particlesFigure 1 | Schematic representation of synthetic strategies for nanoparticles with different architectures (plain, coreshell and hollow) using amphiphilicstar-like block co-polymers as nanoreactors. ac, Formation of plain nanoparticles (a), coreshell nanoparticles (b) and hollow nanoparticles (c). CD,cyclodextrin; BMP, 2-bromo-2-methylpropionate; St, styrene.NATURE NANOTECHNOLOGYDOI: 10.1038/NNANO.2013.85LETTERSNATURE NANOTECHNOLOGY | VOL 8 | JUNE 2013 | www.nature.com/naturenanotechnology 427 2013 Macmillan Publishers Limited.All rights reserved. which nanoparticles nucleate and grow. This mixed solventapproachiskeytoourmethod(Fig. 2c). WhenDMFalonewasusedasthesolvent, PbTiO3nanoparticleshadrelativelyirregularshapes (DMF:benzyl alcohol 10:0 by volume; Fig. 2b, left). Witha 9:1 DMF:benzyl alcohol solvent ratio, PbTiO3nanoparticleswere produced with the best uniformity (Fig. 2b, centre). As morebenzyl alcohol wasadded(DMF:benzyl alcohol 5:5), theshaperegularityof nanoparticles decreasedagain(Fig. 2b, right). Themechanismforthegrowthofnanoparticlesinthemixedsolventsat different volume ratios is illustrated in Fig. 2c.Surprisingly, the strategy for our star-like block co-polymernanoreactorfornanoparticlesynthesisisquitegeneral. It canbereadilyextendedtoproducealargevarietyof nanoparticleswithgooduniformity(withmost of thesizedistributionlyingwithin5% of the average size) and solubility, including noble metal, ferro-electric, magnetic and semiconductor nanoparticles. These differenttypes of nanoparticle are shown in the representative TEM images ofFig. 3 (their crystalline lattices are shown both in the insets to Fig. 3and in Supplementary Fig. S21) and as digital images inSupplementary Fig. S22. The possible mechanisms for formingPbTiO3, TiO2and ZnO nanoparticles are proposed inSupplementaryFigsS2S4. Metallicplatinumnanoparticleswerealso prepared and are shown in Supplementary Fig. S23. Energy-dis-persive spectroscopy (EDS) microanalysis andX-ray diffraction(XRD)measurementsconrmedthesuccessful synthesisofthesematerials(SupplementarySectionSVIII). Thesefunctional nano-particlesareintrinsicallylinkedtoouterhydrophobicPSblocks,imparting good solubility in organic solvents (such as toluene, tetra-hydrofuran (THF), chloroform, dichloromethane, DMF and so on).Furthermore, the presence of hydrophobic PS blocks is also crucialto ensuring the miscibility of nanoparticles with the host environ-ment, retaining the unique properties of the nanoparticles by pre-venting them from aggregating.In many instances it is highly desirable to prepare water-solublenanoparticles connectedwithhydrophilic ligands for use inbiomedicalapplications23. To this end, by changing the template fromamphiphilicstar-like PAA-b-PStoa double-hydrophilic star-like PAA-b-PEOdiblockco-polymersynthesizedbya combinationofatomtransferad110 = 2.76bcDPbTiO3 = ~ 9.8 nm DPbTiO3 = ~ 5.7 nmDPbTiO3 = ~ 16.1 nmVDMF:VBA=10:0 VDMF:VBA= 9:1 VDMF:VBA= 5:5VDMF:VBA= 9:180 nm2 nm100 nm150 nm100 nm 50 nm 120 nmDMF PrecursorsVDMF:VBA=5:5Figure 2 | Formation of plain nanoparticles. a, TEM images of three PbTiO3 nanoparticles with different diameters prepared using three star-like PAA-b-PStemplates with different molecular weights of PAA block as nanoreactors (see also samples AC in Supplementary Table S1). An HRTEM image of the9.8+0.4 nm nanoparticle is shown (lower left), demonstrating a continuous crystalline lattice with a lattice spacing of 2.76 , corresponding to the (110)crystalline plane of the tetragonal phase of PbTiO3, suggesting the formation of a single-crystal structure. b, TEM images of PbTiO3 nanoparticles (sample Ain Supplementary Table S1) formed in a mixture of DMF and benzyl alcohol (BA) at different volume ratios. c, Proposed mechanism for the growth of uniform(VDMF:VBA9:1) and non-uniform (VDMF:VBA10:1 and VDMF:VBA5:5) nanoparticles in DMF and benzyl alcohol. The mechanism for the growth of nearlymonodisperse nanoparticles can be rationalized by considering the solubility of each block in DMF and benzyl alcohol. The star-like PAA-b-PS can be readilydissolved in DMF, forming unimolecular micelles (c, upper left). With the addition of benzyl alcohol, a good solvent for PAA but a non-solvent for PS, theouter PS blocks collapse due to unfavourable interaction between PS and benzyl alcohol, while the inner PAA blocks retain a coil-like conformation.At VDMF:VBA9:1, a transition from the expanded chain conformation in pure DMF (c, upper left) into a more compact and structurally stable sphericalmacromolecule occurs (c, centre left). The density of inner PAA blocks (that is, the number of chains per volume) increases slightly, resulting in smallchain-length shrinkage. This is observed by comparing the TEM image of a with the dynamic-light-scattering measurements in Supplementary Table S7.At the same time, the loading of precursors into this well-dened regime composed of PAA chains increases, yielding nanoparticles with markedly improveduniformity (a and b, centre). However, with the addition of more benzyl alcohol (VDMF:VBA5:5), a signicant collapse of the outer PS chains is observed(c, lower left), making it difcult for precursors to enter the PAA phase, and thus forming non-uniform nanoparticles (b, right).LETTERSNATURE NANOTECHNOLOGYDOI: 10.1038/NNANO.2013.85NATURE NANOTECHNOLOGY | VOL 8 | JUNE 2013 | www.nature.com/naturenanotechnology 428 2013 Macmillan Publishers Limited.All rights reserved. radical polymerization(ATRP) andclickreaction(SupplementarySection SI-1), a series of water-soluble plain nanoparticles (forexample, gold, SupplementaryFig. S26; platinum, SupplementaryFig. S27; andFe3O4, SupplementaryFig. S28)werealsoproducedsuccessfully (Supplementary Scheme S1, Table S2, Section SVII).Of particular interest is the fact that our strategy for producinghighly crystalline nanoparticles is remarkably versatile. In additionto plain nanoparticles, we also synthesized coreshell nanoparticles.Coreshell nanostructures are conventionally obtained by dissimilarmaterials epitaxy, which requires moderate lattice mismatches(,2%) betweenthe twodifferent materials soas toobtainthehigh-qualitycoreshell heterostructures that wouldotherwisebedifcult to achieve24,25.As outlined in Fig. 1b, our general strategy for using a new classof star-liketriblockco-polymersasnanoreactorsenablesthecre-ationof awiderangeof coreshell nanoparticleswithwell-con-trolledsize of the core andshell materials, as well as differentcompositionsandproperties. Possiblenanoparticlecombinationsinclude, but are not limited to, metalsemiconductor orsemiconductormetal, metalmetal oxide or metal oxidemetal,and dissimilarmetal oxide coreshell nanoparticles, as veriedbyXRD measurements (Supplementary Figs S49, S51S53).Similarly, thegrowthofcoreshellnanoparticleswasbasedonthecoordinationreactionbetweenfunctional blocks inthestar-liketriblockco-polymerandtherespectiveprecursors (Fig. 1b).The size of the core and shell materials can be readily tuned by alter-ing the length of the rst P4VP block and the second PtBA block(hydrolysed into PAA later), respectively. More importantly,because the growth of the shell is completely templated by the func-tional secondblockof the triblockco-polymer, the shell latticestructurecanbeindependentofthecorematerial24, thuscircum-venting the limitations imposed with epitaxial growth.We chose the synthesis of coreshell magneticferroelectricFe3O4PbTiO3nanoparticles as an example. The Fe3O4core(Fig. 4a, left) was rst formed by the encapsulation of its precursorswithin the innermost P4VP regime through a selective coordinationinteraction between the nitrogen atoms of the P4VP blocks (Fig. 1b)and the metal moieties of the precursors (see the proposedBaTiO3ZnOAgCdSe TiO2Fe3O4PbTiO3Au50 nm 100 nm100 nm 100 nm 100 nm100 nm 10 nm 5 nm 5 nm5 nm 5 nm 5 nm5 nm 5 nm2 nm2 nm150 nm150 nmCu2OFigure 3 | Representative TEM images of a variety of nanoparticles synthesized using star-like PAA-b-PS templates (samples A, B and D inSupplementary Table S1). The images show noble metal (gold, with surface plasmonic properties, Supplementary Fig. S18; silver), ferroelectric (PbTiO3 andBaTiO3), magnetic (Fe3O4, exhibiting superparamagnetic properties, Supplementary Fig. S19) and semiconductor (n-type ZnO, n-type TiO2; luminescentCdSe, showing optical properties, Supplementary Fig. S20; p-type Cu2O) nanoparticles. Diameters of nanoparticles: noble metal (DAu5.8+0.2 nm,DAg6.1+0.3 nm); ferroelectric (DPbTiO39.7+0.4 nm, DBaTiO310.4+0.3 nm); magnetic (DFe3O410.1+0.5 nm); and semiconductor (DZnO6.3+0.3 nm,DTiO210.2+0.2 nm, DCdSe6.2+0.3 nm, DCu2O6.4+0.2 nm). Insets: the crystalline lattices of each nanoparticle are clearly evident in HRTEM images.Corresponding digital images of the nanoparticles are shown in Supplementary Fig. S22. Digital images of CdSe nanoparticles before (left) and after (right,emitting red uorescence) ultraviolet illumination are shown as insets (bottom, centre).NATURE NANOTECHNOLOGYDOI: 10.1038/NNANO.2013.85LETTERSNATURE NANOTECHNOLOGY | VOL 8 | JUNE 2013 | www.nature.com/naturenanotechnology 429 2013 Macmillan Publishers Limited.All rights reserved. formationmechanisminSupplementaryFig. S5)14. Subsequently,the PtBA blocks situated on the surface of the Fe3O4 core were ther-mally hydrolysed into PAA(Supplementary Section SIII). ThePbTiO3 shell was then formed by using the PAA blocks as a tem-plate(SupplementaryFig. S6). Figure4bpresentsTEMimagesofFe3O4PbTiO3 nanoparticles (Fig. 4b, upper panels) with uniformsizeandnarrowsizedistribution. ThecrystallinePbTiO3shell isclearly evident in the HRTEMimage in Fig. 4b (lower left;3.1+0.3 nmthick). Thecrystal structures of Fe3O4andPbTiO3were further corroborated by XRD and EDS measurements(SupplementaryFigs S52, S67). Strikingly, despitemorethan 40%latticemismatch between Fe3O4 and PbTiO3 (ref. 24),the Fe3O4PbTiO3nanoparticles were successfully synthesized using ourstar-like triblock co-polymer template strategy. Similarly, othercoreshell nanoparticles can also be produced as long as appropriateprecursors are identied (for example, Fe3O4Au in SupplementaryFigs S5, S7, S29, and AuCdSe in Supplementary Fig. S30).In addition to organic solvent-soluble coreshell nanoparticles,water-soluble coreshell nanoparticles can also be produced.Usingatriple-hydrophilicstar-likeP4VP-b-PAA-b-PEOtriblockco-polymer (Supplementary Section SI-2) as the nanoreactor,water-soluble coreshell nanoparticles (for example, Fe3O4Au,Supplementary Fig. S31; base metalnoble metal SnPt,SupplementaryFig. S32), intimatelyconnectedwithhydrophilicPEOblocks, werecreated(SupplementarySchemeS2, TableS4,Section SVII).Interestingly, amphiphilic star-like triblock co-polymers can alsobe used to structure-direct precursors into hollow, nearly monodis-perse nanoparticles byselectivelysequesteringprecursors intheintermediate block and growing into nanoparticles. Hollow noble-metal nanoparticlesarethesubjectofintenseresearchforuseinbioimaging, photothermal therapy and drug delivery26. We preparedhollowgoldnanoparticlesusingourstar-likePS-b-PAA-b-PStri-block co-polymer template (Supplementary Table S5, SectionSI-3). The gold precursors were conned in the intermediate PAAregime (Fig. 1c), and ultimately yielded hollow gold nanoparticleswith hydrophobic PS blocks intimately tethered on both theinsideandoutsideof thegoldsurface. Notably, membersof thisintriguing class of nanoparticles may be regarded as organicinor-ganic coreshellnanoparticles(for example, with a PScoreand agold shell).It isnot surprisingthat TEMcharacterizationclearlydemon-stratedthat thegoldnanoparticles weremorphologicallyhollow,appearingbright intheircentre(Fig. 4c). Thehighlycrystallinenature of the hollownanoparticles is apparent inthe HRTEMimage, wherethecrystallinelatticepartially appearsinthecentre.This can be attributed to the presence of the crystalline gold shellabove and below the hollow core. Moreover, the compositionandelemental distributionof hollowstructuresmappedbyEDSandXRDmeasurements further provedthe successful formationofhollowgoldnanoparticles(forexample, SupplementaryFig. S56).The size of such hollow nanoparticles can be conveniently0 min 2 min 10 minMagnet Magnetab0 min 10 minMagnetcFe3O4 core Coreshell Fe3O4PbTiO3Fe3O4PbTiO3HollowHollow100 nm 100 nm100 nm50 nm 5 nm15 nm5 nm50 nmFigure 4 | TEM and digital images of Fe3O4PbTiO3 coreshell nanoparticles and TEM images of hollow gold nanoparticles formed using star-like triblockco-polymers as nanoreactors. a,b, TEM images of Fe3O4 core (a, DFe3O46.1+0.3 nm) and Fe3O4PbTiO3 coreshell nanoparticles at differentmagnications (b, PbTiO3 shell thickness 3.1+0.3 nm). Fe3O4 appears dark. An HRTEM image (lower left panel, b) clearly shows the crystalline lattices ofthe Fe3O4 core and PbTiO3 shell (white and black dashed circles for guidance). The magnetic properties of the Fe3O4PbTiO3 nanoparticles were retained, asclearly shown in the digital images of a nanoparticle toluene solution, which show the nanoparticles deposited on the wall of the vials under the inuence ofmagnetic bars (marked with black boxes) (a, central, t 2 min; right, t 10 min). For Fe3O4 core materials only, the toluene solution appears dark at highconcentrations, resulting from the Fe3O4 (a, left, t 0 min). For Fe3O4PbTiO3 coreshell nanoparticles, the toluene solution appears white, resulting fromthe PbTiO3 shell (b, left, t 0 min). c, TEM images of representative hollow gold nanoparticles with a uniform size distribution (thickness of gold,3.2+0.3 nm; diameter of hollow core, 5.6+0.4 nm).LETTERSNATURE NANOTECHNOLOGYDOI: 10.1038/NNANO.2013.85NATURE NANOTECHNOLOGY | VOL 8 | JUNE 2013 | www.nature.com/naturenanotechnology 430 2013 Macmillan Publishers Limited.All rights reserved. controlledbyvaryingthelengthof theinnermost PSblockandintermediate PtBA block during ATRP, thus allowing for the pro-ductionof avarietyof hollownanoparticleswithdifferent sizes,including hollow semiconductor Cu2O nanoparticles(Supplementary Fig. S33). Similarly, water-soluble hollow nanopar-ticles (for example, gold, Supplementary Figs S34, S57) linked withhydrophilic PEOblocks can also be produced using star-likePS-b-PAA-b-PEO triblock co-polymer as the nanoreactor(Supplementary Scheme S3, Table S6, Section SVII).Theunimolecularmicelle-templatestrategywehavedescribedenables the synthesis of nearly monodisperse nanoparticles with pre-cisely controllable size and surface chemistry, and including plain,coreshellandhollownanostructures. Thepermanentconnectionbetween the nanoparticles and the respective hydrophobic or hydro-philicpolymerchains rendersthemsolubleineitherorganicoraqueousenvironments, respectively. Ourapproachcanbereadilyextended to nearly all the transition or main-group metal ions andorganometallic ions. We envisage that more complex nanoparticleswith multifunctional shells (for example, coreshell 1shell 2,coreshell 1shell 2shell 3) may also be made using star-like tetra-block and pentablock co-polymer templates, with the possibility ofcraftingdesiredarbitrarynanostructuresforfundamental studiesin nanoscience. Finally, in addition to inorganic colloidal nanocrys-tals, the method we have reported may also be viable for the synthesisof polymeric nanoparticles by selectively crosslinking intermediateblocksof star-likeblockco-polymers, suggestingpotential appli-cations as nanocapsules for the release of drugs, inks and so on1,26.MethodsSynthesis of nanoparticles using star-like block co-polymers as nanoreactors. Forplain nanoparticles, 10 mg star-like PAA-b-PS template was dissolved in a 10 mlmixture of DMF and benzyl alcohol at room temperature (VDMF:VBA9:1),followed by the addition of appropriate amounts of precursors (for example,PbTi[OCH(CH3)2]6) that were selectively incorporated into the inner PAA blocks.The molar ratio of acrylic acid (AA) units in the PAA block to precursor was set at1:5 to maximize the loading of precursors into the PAA domains. The mixture wasthen reuxed at elevated temperature for a period of time (for example, 180 8C for2 h for PbTiO3). For coreshell nanoparticles, 10 mg star-like P4VP-b-PtBA-b-PStemplate was dissolved in a 10 ml mixture of DMF and benzyl alcohol at roomtemperature (VDMF:VBA9:1). The core material was rst formed by theencapsulation of its precursors (for example, FeCl2.4H2O:FeCl3.6H2O:ammoniumhydroxide 1:1:1 by mole for Fe3O4) within the innermost P4VP regime, followedby reaction at a certain temperature for a period of time (for example, 50 8C for30 min for Fe3O4). Similarly, the molar ratio of the 4-vinylpyridine (4VP) unit of theP4VP block to precursors was 1:5. Subsequently, the PtBA blocks were hydrolysedinto PAA by annealing in phenyl ether at 200 8C for 2 h. The shell materials werethen formed by carrying out the reaction (for example, reuxing at 180 8C for 2 h forPbTiO3 using PbTi[OCH(CH3)2]6 as precursor) with the use of PAA blocks astemplate while keeping the other experimental conditions the same. For hollownanoparticles, 10 mg star-like PS-b-PAA-b-PS template was dissolved in a 10 mlmixture of DMF and benzyl alcohol at room temperature (VDMF:VBA9:1).Similarly, the precursor (for example, HAuCl4) and reducer (such as ethanol, ifapplicable) were subsequently added into the template solution. After the reaction(for example, at 60 8C for 10 h for gold), hollow nanoparticles (for example, gold)with PS blocks tethered on both the inside and outside were obtained (seeSupplementary Section SVII for experimental details). For the synthesis of water-soluble nanoparticles (plain, coreshell and hollow) linked with hydrophilic PEOblocks, see Supplementary Section SVII.Synthesis of nanoparticles using linear block co-polymers as templates. Tocompare the use of star-like block co-polymers with linear block co-polymercounterparts as nanoreactors for the synthesis of nanoparticles under the sameexperimental conditions, linear block co-polymers (PAA-b-PS, P4VP-b-PtBA-b-PSand PS-b-PAA-b-PS) with similar molecular weights and ratios of the differentblocks to those of star-like block co-polymers were also synthesized by ATRP.Instead of nanoparticles like those produced using star-like block co-polymertemplates, large irregular aggregates were formed when the corresponding linearblock co-polymers were used as templates in the mixture of DMF and benzyl alcohol(VDMF:VBA9:1). A detailed comparison (a mechanistic study) is presented inSupplementary Section SX.Received 10 December 2012; accepted 12 April 2013;published online 2 June 2013References1. Langer, R. Drug delivery and targeting. Nature 392, 510 (1998).2. Wang, X., Zhuang, J., Peng, Q. & Li, Y. A general strategy for nanocrystalsynthesis. Nature 437, 121124 (2005).3. 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Tsukruk for helpful discussions.Author contributionsZ.L. and X.P. conceived and designed the experiments. X.P., L.Z., W.H. and X.X. performedthe experiments. Z.L., X.P., L.Z., W.H. and X.X. analysed the data. Z.L., X.P. and L.Z.wrote the paper. All authors discussed the results and commented on the manuscript.Additional informationSupplementary information is available in the online version of the paper. Reprints andpermissions information is available online at www.nature.com/reprints. Correspondence andrequests for materials should be addressed to Z.L.Competing nancial interestsThe authors declare no competing nancial interests.NATURE NANOTECHNOLOGYDOI: 10.1038/NNANO.2013.85LETTERSNATURE NANOTECHNOLOGY | VOL 8 | JUNE 2013 | www.nature.com/naturenanotechnology 431 2013 Macmillan Publishers Limited.All rights reserved.