Synthesis of a Multifunctional Nanocomposite with Magnetic, Mesoporous, and Near-IR

Synthesis of a Multifunctional Nanocomposite with Magnetic,Mesoporous,and Near-IR Absorption PropertiesZhenhe Xu,Chunxia Li,*Xiaojiao Kang,Dongmei Yang,Piaoping Yang,Zhiyao Hou,andJun Lin*State Key Laboratory of Rare Earth Resource Utilization,Changchun Institute of Applied Chemistry,ChineseAcademy of Sciences,Changchun130022,People's Republic of China,and Graduate Uni V ersity of the ChineseAcademy of Sciences,Beijing100049,People’s Republic of ChinaRecei V ed:July8,2010;Re V ised Manuscript Recei V ed:August23,2010In this work,we report a multifunctional inorganic nanocomposite which is composed of mesoporous silicacoated ferrite core and numerous gold nanoparticles(NPs)support on the surface of mesoporous silica.X-raydiffraction,scanning electron microscopy,transmission electron microscopy,energy-dispersive X-ray,X-rayphotoelectron spectra,Fourier transform infrared spectroscopy,UV-vis spectroscopy,N2adsorption/desorption,superconducting quantum interference device were used to characterize the samples.The results indicatedthat the nanocomposites show typical ordered mesoporous characteristics(2.4nm)and high magnetization(46.3emu/g),thus it is possible for drug targeting under a foreign magneticfield.In addition,the Au NPs’shell,coated mesoporous silica containing ferrite cores,exhibits near-infrared absorption(suitable forphotothermal therapy).A drug release test indicates that the multifunctional system shows drug-sustainedproperties with ibuprofen as the model drug.This multifunctional system has potential for targeting drugdelivery and photothermal therapy based on all the properties they possess.1.IntroductionThe synergistic combination of nanotechnology and biotech-nology has developed into an emerging and interdisciplinary research area:nanobiotechnology.1The design and synthesis of multifunctional nanomedical platforms that integrate suitably multiple nanomaterials with different properties into a single nanosystem provides unparalleled opportunity for simultaneous diagnostics and therapy of diseases.2In particular,the construc-tion of multicomponent hybrid nanostructures that contain magnetic Fe3O4and Au components has been a research hotspot in the forefront of materials science,because Fe3O4nanoparticles have important biomedical applications ranging from magnetic resonance imaging(MRI)and biomolecular separation to targeted drug/gene delivery.Alternatively,Au nanoparticles are extensively exploited in plasmon-based labeling and imaging, optical and electrochemical sensing,diagnostics,and therapy for various diseases due to their excellent stability and biocom-patibility.3So the combination of Fe3O4and Au nanopaticles in a single nanocomposite endows these kinds of materials with beneficial prospects in MRI diagnosis,target delivery,and NIR photothermal therapy.4However,the construction of nanocom-posites,direct coating of magnetic particles with gold is a difficult task due to the dissimilar nature of the two surfaces.5 So one of the promising and popular strategies is to choose an appropriate linker to elaborately form core-shell structures.So far,polymers and silica are the most common and important linkers to bridge these two nanoparticles.For example, Fe3O4@PAH@Au,6Fe3O4@PPy@Au,7Fe3O4@Polyaniline@Au,8 and Fe3O4@SiO2@Au,9core-shell structured multifunctional nanocomposites have been successfully obtained.However, these reported hybrid composites are nonporous,and little attention has been paid to the integration of mesoporous silica with Fe3O4and Au in order to realize multivarious objectives for simultaneous bioimaging and drug/gene delivery.10It is well-known that ordered mesoporous silica materials have been the subject of intensive research,due to their unique properties including stable mesoporous structure,tunable pore size,high specific surface area,easily modifiable surface,and good compatibility,which endow them with great potential applica-tions in thefields of catalysis,sensing,and optically active materials.11,12Therefore,the integration the mesoporous silica with Fe3O4and Au is undoubtedly of great importance in multimodal bioimaging,bioseparation,controlled drug release, and photothermal therapy.In this work,we present a multistep procedure for synthesiz-ing multifunctional nanocomposites composed of spherical silica-coated Fe3O4core further coated with an ordered meso-porous silica shell,followed by coating with colloidal Au nanoparticles.We also demonstrate the multiple properties of these core-shell-structured nanocomposites with magnetization, mesoporous,near-infrared(NIR)absorption,as well as the loading and controlled release of drug molecules.2.Experimental Section2.1.Synthesis of Magnetic Fe3O4Nanoparticles.All of the chemical agents used in this experiment were of analytical grade and used directly without further purification.Typically, FeCl3·6H2O(4.04g)and sodium acetate(8.20g)were quickly added into a mixed solution of ethylene glycol(100mL).After being vigorously stirred for30min,the obtained solution was transferred to a Teflon-lined stainless-steel autoclave and heated at200°C for8h.The autoclave was then naturally cooled to room temperature.The obtained black magnetite particles were washed with ethanol and deionized water in sequence and dried in vacuum at60°C for24h.*To whom correspondence should be addressed.E-mail:cxli@(C.X.L.)and jlin@(J.L.).J.Phys.Chem.C2010,114,16343–163501634310.1021/jp106325c 2010American Chemical SocietyPublished on Web09/09/20102.2.Synthesis and Functionalization of Fe3O4@nSiO2@ mSiO2Nanocomposites.In a typical procedure,as-prepared Fe3O4(0.10g)nanoparticles were treated with ethanol by ultrasonication for30min.Subsequently,the treated nanopar-ticles were separated by centrifugation,and then well dispersed in a mixture of ethanol(80mL),deionized water(20mL),and concentrated ammonia aqueous solution(28wt%,1.0mL). TEOS(0.03g)was then added dropwise to the solution.After being stirred for6h,the products were separated using a magnet and washed with ethanol and water,and then redispersed in a mixed solution containing cetyltrimethylammonium bromide (CTAB)(0.3g),deionized water(80mL),concentrated am-monia aqueous solution(28wt%,1.2mL),and ethanol(60 mL).The resulting solution was stirred for30min.TEOS(0.4 g)was then added dropwise to the solution with stirring.After being stirred for another6h,the products were collected and separated with a magnet,washed with ethanol and water several times,and dried in air at80°C for24h.The above coating process was repeated twice.The structure-directing agent (CTAB)was subsequently removed by a reflux method.Briefly, the as-prepared sample(0.6g)containing CTAB was dispersedin acetone(120mL)and refluxed at75°C in an oil bath for 48h,and then washed with acetone twice.The above CTAB-removal process was repeated three times.2b Finally,the CTAB-removed product was dried in air at80°C for12h and denoted as Fe3O4@n SiO2@m SiO2.For APTS-functionalized Fe3O4@n SiO2@m SiO2nanocom-posites,Fe3O4@n SiO2@m SiO2nanocomposites(20mg)were added to ethanol(30mL),followed by the addition of water(2 mL).Then,ammonium hydroxide(25%;2mL)and APTS(200µL)were added to the above solution.The resulting solution was sonicated for about2h at80°C.After four-step separation by means of an external magneticfield,the resulting product was dissolved in water(10mL).2.3.Synthesis of Au Nanoparticles.A1mM HAuCl4 solution(100mL)was brought to reflux while being stirred and then38.8mM trisodium citrate solution(10mL)was quickly added,which resulted in a color change of the solution from pale yellow to deep red.The solution was then heated to reflux for an additional15min.The concentration of Au nanoparticles was about1mM provided that HAuCl4was completely reduced.2.4.Constructing Fe3O4@nSiO2@mSiO2@Au Nanocom-posites.The core-shell structured Fe3O4@n SiO2@m SiO2@Au nanocomposite was prepared by mixing an aqueous solution of APTS-functionalized Fe3O4@n SiO2@m SiO2@nanospheres(1 mL)with10-20mL of a solution of Au nanoparticles(excess). The resulting products were collected by means of an external magnet and dissolved in1mL of water.2.5.Preparation of Drug Storage/Delivery Systems.The drug storage/release system using the core-shell structured Fe3O4@n SiO2@m SiO2@Au nanocomposites as a carrier was prepared according to previous reports.13Ibuprofen(IBU)was selected as the model drug.Typically,0.2g of the core-shell structured Fe3O4@n SiO2@m SiO2@Au nanocomposites sample was added into30mL of hexane solution with the IBU concentration of60mg mL-1at room temperature,and soaked for24h with stirring in a vial that was sealed to prevent the evaporation of hexane.The IBU-loaded sample was separated by centrifugation,and then dried in vacuum at60°C for24h, and denoted as IBU-Fe3O4@n SiO2@m SiO2@Au.The in vitro delivery of IBU was performed by immersing 0.2g of the sample in the release media of simulated bodyfluid (SBF)with slow stirring under the immersing temperature of 37°C.The ionic composition of the as-prepared SBF solution was similar to that of human body plasma with a molar composition of142.0/5.0/2.5/1.5/147.8/4.2/1.0/0.5for Na+/K+/ Ca2+/Mg2+/Cl-/HCO3-/HPO42-/SO42-(pH)7.4).The ratio of SBF to adsorbed IBU was kept at1mL mg-1.At selected time intervals,a sample(0.5mL)was removed and immediately replaced with an equal volume of fresh SBF.The solution removed was properly diluted and the amount of ibuprofen present was monitored at222nm using a UV-vis spectropho-tometer.2.6.Characterization.Powder X-ray diffraction(XRD) measurements were performed on a Rigaku-Dmax2500dif-fractometer with Cu K R radiation(λ)0.15405nm).FT-IR spectra were obtained using Perkin-Elmer580B infrared spectrophotometer using the KBr pellet technique.The mor-phology and composition of the samples were inspected using a scanning electron microscope(SEM;S-4800,Hitachi). Transmission electron microscopy(TEM)and high-resolution transmission electron microscopy(HRTEM)micrographs were obtained from an FEI Tecnai G2S-Twin transmission electron microscope with afield emission gun operating at200kV. Nitrogen adsorption/desorption analysis was measured using a Micromeritics ASAP2020M apparatus.The specific surface area was determined by the Brunauer-Emmett-Teller(BET) method using the data between0.05and0.35.The X-ray photoelectron spectra(XPS)were taken on a VG ESCALAB MK II electron energy spectrometer using Mg Ka(1253.6eV) as the X-ray excitation source.The UV-vis adsorption spectral values were measured on a TU-1901spectrophotometer. Magnetization measurements were performed on a MPM5-XL-5 superconducting quantum interference device(SQUID)mag-netometer at300K.All of the measurements were performed at room temperature.3.Results and DiscussionThe synthesis process of such multifunctional Fe3O4@ n SiO2@m SiO2@Au core-shell-structured nanocomposite is presented in Scheme1.First,the Fe3O4nanospheres with high saturation magnetization were synthesized by a solvothermal process.14Scanning electron microscopy(SEM)images of the magnetite particles confirm the uniform size of about300nm and nearly spherical shape with rough surface(Figure1A,B). The surface roughness is attributed to the fact that the particles SCHEME1:Formation Process of MultifunctionalFe3O4@n SiO2@m SiO2@Au Nanocomposites16344J.Phys.Chem.C,Vol.114,No.39,2010Xu etal.are formed by packing of a lot of nanoparticles.Figure 1C shows a typical transmission electron microscopy (TEM)image of monodisperse Fe 3O 4nanospheres with a relatively rough surface and an average diameter of 300nm,consistent with the SEM results.Selected-area electron diffraction reveals that the particles have a polycrystalline feature (Figure 1C,inset).The citrate-stabilized Au nanoparticles were prepared according to the procedures in the literature,15which have the size of ∼13nm in diameter (Figure 1D).Second,mesoporous silica shell offers many advantages as the framework for the multifunctional nanoparticles.Mesoporous silica shell (50nm)was synthesized around the iron oxide nanospheres by following a modification of the procedures described by Zhao et al.16In this procedure,Fe 3O 4particles were first modified with SiO 2through a modified Sto ¨ber procedure,17to result in the formation of the silica-Fe 3O 4composites with a nonporous silica layer of 5nm in thickness (denoted as Fe 3O 4@n SiO 2),as shown in Figure 2.Subsequently,cetyltrimethylammonium bromide (CTAB)was selected as the organic template for the formation of the outer mesoporous silica layer on Fe 3O 4@n SiO 2.The subsequent treatment with refluxing acetone could remove CTAB templates and lead to a uniform mesoporous silica shell.The CTAB-removed sample was designated as Fe 3O 4@n SiO 2@m SiO 2.The SEM image (Figure 3A)shows that the Fe 3O 4@n SiO 2@m SiO 2microspheres still keep the morphological properties of pure Fe 3O 4except for a slightly larger particle size about 350nm,which is caused by the coating of nonporous silica through a sol -gel approach and further deposition of mesoporous silica on the surface of the magnetic core.2b Interestingly,the Fe 3O 4@n SiO 2@m SiO 2mi-crospheres exhibit much smoother surface than that of pure Fe 3O 4,further confirming the uniform coating of silica shell.The morphological and structural features of the Fe 3O 4@n SiO 2@m SiO 2microspheres were further examined by TEM.The core -shell structure can be clearly distinguished because of the different electron penetrability between the cores and shells (Figure 3B).The magnetic cores are black spheres with an average size of around 300nm,and the silica shell shows a gray color with an average thickness of about 50nm.Notably,quasi hexagonal mesopore channels are clearly found to be perpendicular to the spheres’surface (Figure 3C,D).2b Finally,in order to attach Au nanoparticles,the Fe 3O 4@n SiO 2@m SiO 2particles were functionalized with NH 2groups by condensation reaction of OH groups on the surface of the Fe 3O 4@n SiO 2@m SiO 2spheres and 3-aminopropyltriethoxysilane (APTS).These APTS-functionalized Fe 3O 4@n SiO 2@m SiO 2magnetite micro-spheres were then mixed with the citrate-stability Au nanopar-ticles,and the Au nanoparticles were confined on the surface of the Fe 3O 4@n SiO 2@m SiO 2spheres via strong coordination and static interactions.As shown in Figure 4A,many small Au nanoparticles (13nm)are closely and evenly immobilized on the surface of the polymer-coated Fe 3O 4@n SiO 2@m SiO 2sur-face.The enlarged image (Figure 4B)reveals the feature of dense and discontinuous surface coverage of Au shell.The corresponding TEM images (Figure 4C)further support the above statement.A magnified image (Figure 4D)shows that high-density Au nanoparticles are efficiently adsorbed on the surface of the Fe 3O 4@n SiO 2@m SiO 2spheres and the quasi hexagonal mesopore channels are well preserved.The EDX characterization demonstrates that the particles contain three necessary and diagnostic elements of the precursors,Fe,Si,and Au (Figure 4E).Wide-angle X-ray diffraction (XRD)patterns of the pure Fe 3O 4,Fe 3O 4@n SiO 2@m SiO 2,and Fe 3O 4@n SiO 2@m SiO 2@Au samples are displayed in Figure 5.For Fe 3O 4(Figure 5A),the diffraction peaks can be readily indexed to a face-centered cubic structure (Fd3m space group)of magnetite according to JCPDSFigure 1.SEM (A,B)and TEM (C)images of the Fe 3O 4particles as well as TEM (D)images of Au nanoparticles.Inset (C)is the SAED pattern record on single particle.Synthesis of a Multifunctional Nanocomposite J.Phys.Chem.C,Vol.114,No.39,201016345card No.19-0629.In the case of Fe 3O 4@n SiO 2@m SiO 2@Au (Figure 5C),besides the characteristic diffractions of cubic Fe 3O 4,the obvious diffraction peaks at 2θ)38.2°,44.4°,64.6°,and 77.8°can be indexed to the cubic-phase Au,further suggesting the successful attachment of Au nanoparticles and well-retained magnetite phase.XPS has been utilized as a usefulFigure 2.SEM (A,B)and TEM (C,D)images of the Fe 3O 4@n SiO 2.Figure 3.SEM (A)and TEM (B -D)images of the Fe 3O 4@n SiO 2@m SiO 2.16346J.Phys.Chem.C,Vol.114,No.39,2010Xu etal.tool for qualitatively determining the surface component and composition of a sample.The survey and the respective element XPS of Fe 3O 4@n SiO 2@m SiO 2@Au are given in Figure 6.Figure 6A shows the survey XPS spectrum of the as-prepared sample in a binding energy range of 0-1200eV.The XPS narrow scan spectra of Fe 2p,Si 2p,and Au 4f core level peaks are shown in Figure 6B -D.The XPS spectrum indicates that the main peaks at 711.1,723.8,102.8,83.5,and 87.2eV can be assigned readily to the binding energy of Fe 2p,Si 2p,and Au 4f,respectively,which further supports the above conclusion that the surface of the Fe 3O 4@nSiO 2@mSiO 2particles has been functionalized with Au nanoparticles.The FT-IR spectra of (A)Fe 3O 4@n SiO 2@CTAB/SiO 2with-out the treatment of acetone,(B)Fe 3O 4@n SiO 2@m SiO 2,(C)IBU-Fe 3O 4@n SiO 2@m SiO 2@Au,and (D)pure IBU are shown in Figure 7.In the FT-IR spectrum of Fe 3O 4@n SiO 2@m SiO 2(Figure 7B),the strong bands of OH (3439cm -1)and H 2O (1642cm -1)suggest that a large number of OH groups and H 2O molecules exist on the surface,which plays a key role for adsorbing IBU molecules by hydrogen bond.The absorption bands related with Si -O -Si (1080cm -1and 806cm -1),Si -OH (955cm -1),Si -O (458cm -1),and Fe -O (587cm -1)can also be observed.For IBU loaded IBU-Fe 3O 4@n SiO 2@m SiO 2@Au (Figure 7C),the band assigned to -COOH (1720cm -1)is apparent except for a slight intensity decrease compared with pure IBU (Figure 7D).Moreover,the absorption bands of the quaternary carbon atom at 1461and 1518cm -1,tertiary carbonFigure 4.SEM (A,B)and TEM (C,D)images of the Fe 3O 4@n SiO 2@m SiO 2@Au nanocomposites as well as the energy-dispersive X-ray spectroscopy (E)analysis of the nanocomposites.Figure 5.The wide-angle XRD patterns of (A)Fe 3O 4particles,(B)Fe 3O 4@n SiO 2@m SiO 2microshperes,and (C)Fe 3O 4@n SiO 2@m SiO 2@Au nanocomposites.Synthesis of a Multifunctional Nanocomposite J.Phys.Chem.C,Vol.114,No.39,201016347atom at1338cm-1,and C-H x bond at2890cm-1are alsoclear,18confirming the successful incorporation of IBU onto the surface of the outer mesoporous silica.The low-angle XRD pattern(Figure8)of Fe3O4@n SiO2@ m SiO2@Au shows an ordered2D mesopore symmetry,which suggests the short-range ordering character of the sample.The N2adsorption/desorption isotherm of Fe3O4@n SiO2@m SiO2@ Au exhibit typical IV-type isotherms with H1-hysteresis loops (Figure9),which indicates the presence of textual mesopores. The Brunauer-Emmett-Teller(BET)surface area,average pore size,and total pore volume are calculated to be273m2g-1,2.4 nm,and0.17cm3g-1,respectively.The magnetic properties of the microspheres were characterized using a superconducting quantum interference device(SQUID)magnetometer measured at300K.Magnetic measurement shows(Figure10)that pure Fe3O4,Fe3O4@n SiO2@m SiO2,and Fe3O4@n SiO2@m SiO2@Au, have magnetization saturation values of80.7,52.7,and46.3emu/g,respectively.It should be noted that the multifunctional nanocomposite still shows strong magnetization,which suggests its suitability for magnetic separation and targeting.19Upon placement of a magnet beside the vial,materials were quickly attracted to the side of the vial within a few seconds,leaving the solution transparent(Figure10,inset),which illustrates their magnetic nature,and the particles can be well redispersed again by shaking and ultrasonic vibration.UV-vis absorption spectroscopy experiments were carried out to confirm that the as-prepared Fe3O4@nSiO2@mSiO2@Au nanocomposites display the NIR absorption of Au nanoparticles (Figure11).All samples were dispersed in deionized water for the absorption experiments.UV-vis absorption spectra(curve A)shows a plasmon resonance band at522nm,characteristic of the Au nanoparticles with the size of13nm in aqueous solution.20It is clear that the absorption spectrum of Fe3O4Figure6.XPS spectrum of the as-prepared Fe3O4@n SiO2@m SiO2@Au nanocomposites:(A)wide scan spectrum,(B)Fe2p,(C)Si2p,and(D) Au4f.Figure7.FT-IR spectra of(A)Fe3O4@n SiO2@CTAB/SiO2withoutthe treatment of acetone,(B)Fe3O4@n SiO2@m SiO2,(C)IBU-Fe3O4@n SiO2@m SiO2@Au,and(D)pure IBU.Figure8.Low-angle XRD pattern of the Fe3O4@n SiO2@m SiO2@Au nanocomposites.16348J.Phys.Chem.C,Vol.114,No.39,2010Xu etal.particles shows an absorption peak around560nm(curve B) without the absorption in the NIR region.After deposition of the gold nanoparticles on the Fe3O4@n SiO2@m SiO2surface (curve C),the plasmon resonance band is obviously red-shifted from560to810nm and broadened,which is attributable to the strong interactions and coupling of the surface plasmons between neighboring gold nanoparticles.21One of the beneficial prospects of mesoporous silica nano-particles(MSNs)is drug delivery because MSNs are noncyto-toxic,and are able to carry a high payload of guest molecules within the nanopores.22To study the drug storage and release properties of this system as a candidate of drug carriers,IBU was selected as a model drug,which has been extensively investigated for sustained and controlled drug delivery due to its short biological half-life(2h),good pharmacological activity and the suitable molecule size(1.0×0.6nm).Ibuprofen was absorbed onto the surface of the samples with silanol groups and amino groups for the APTS,and released via a diffusion-controlled mechanism.23The loading amount of IBU in IBU-Fe3O4@n SiO2@m SiO2@Au was determined to8wt%.The decrease of IBU loading can be ascribed to the reduction of surface area by the surface modification.The cumulative drug release profiles of this multifunctional system versus release time in SBF are depicted in Figure12.It can be seen that the IBU-Fe3O4@n SiO2@m SiO2@Au systems show a release of over50% within5h,and more than95%of the adsorbed IBU has been released within85h,indicating a sustained property for the ample.The initial sharp burst release may be caused by the rapid leaching of free IBU from the outer surfaces or pore entrances,and the slow release of the rest of IBU can be attributed to the strong interaction between the COOH groups of IBU and the introduced NH2groups.4.ConclusionsWe have demonstrated a successful synthesis of a multifunc-tional Fe3O4@n SiO2@m SiO2@Au core-shell structured nano-composites by combining the sol-gel process,surfactant-assistant approach,and interfacial deposition.The as-prepared core-shell-structured material possesses a high magnetization saturation value(46.3emu/g),ordered hexagonal mesopores(2.4 nm),and near-IR absorption properties.This multifunctional nanocomposite can be potentially used as a targeted drug-delivery and photothermal therapy system.Figure9.N2adsorption/desorption isotherm of Fe3O4@n SiO2@m SiO2@Au nanocomposites.The inset shows the pore size distribution curve obtained from the adsorption data.Figure10.The magnetic hysteresis loops of pure(a)Fe3O4,(b) Fe3O4@n SiO2@m SiO2,and(c)Fe3O4@n SiO2@m SiO2@Au.The inset is the separation process of the Fe3O4@n SiO2@m SiO2@Au nanocom-posites by a magnet.Figure11.UV-vis spectra of(A)colloidal Au solution,(B)Fe3O4 nanoparticles,and(C)Fe3O4@n SiO2@m SiO2@Au nanocomposites. Figure12.Cumulative IBU release from IBU-Fe3O4@nSiO2@ mSiO2@Au system as a function of release time in the release media of SBF.Synthesis of a Multifunctional Nanocomposite J.Phys.Chem.C,Vol.114,No.39,201016349Acknowledgment.This project isfinancially supported by National Basic Research Program of China(2007CB935502, 2010CB327704),and the National Natural Science Foundation of China(NSFC50702057,50872131,20901074,and20921002). References and Notes(1)(a)Yong,K.-T.;Roy,I.;Swihart,M.T.;Prasad,P.N.J.Mater. Chem.2009,19,4655.(b)Gao,J.H.;Gu,H.W.;Xu,B.Acc.Chem.Res. 2009,42,1097.(2)(a)Kim,J.;Piao,Y.Z.;Hyeon,T.Chem.Soc.Re V.2009,38,372.(b)Gai,S.L.;Yang,P.P.;Li,C.X.;Wang,W.X.;Dai,Y.L.;Niu,N.; Lin,J.Ad V.Funct.Mater.2010,20,1166.(3)(a)Boisselier,E.;Astruc,D.Chem.Soc.Re V.2009,38,1759.(b) Kuo,W.S.;Chang,C.N.;Chang,Y.T.;Yang,M.H.;Chien,Y.H.;Chen, S.J.;Yeh,C.S.Angew.Chem.,Int.Ed.2010,49,2711.(c)Wang,C.G.; Irudayaraj,J.Small2010,6,283.(4)(a)Stoeva,S.I.;Huo,F.W.;Lee,J.S.;Mirkin,C.A.J.Am.Chem. 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