Colloids and Surfaces B: Biointerfaces 103 (2013) 326– 344
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Colloids and Surfaces B: Biointerfaces
jou rna l h om epa g e: www.elsev ier .com/ locate /co lsur fb
ortraits of colloidal hybrid nanostructures: Controlled synthesis and potentialpplications
hanh-Dinh Nguyen ∗
epartment of Chemical Engineering, Laval University, Quebec G1K 7P4, Canada
r t i c l e i n f o
rticle history:eceived 1 July 2012eceived in revised form 28 October 2012ccepted 29 October 2012vailable online 12 November 2012
eywords:anohybridatalystnergy conversionurface functionalizationioconjugationiomedical diagnosis and therapy
a b s t r a c t
Inorganic hybrid nanostructures containing two or more nanocomponents have been emerging in manyareas of materials science in recent years. The particle–particle interactions in a hybrid particle sys-tem could significantly improve existing local electronic structure and induce tunable physiochemicalresponses. The current work reviews the diverse inorganic hybrid nanostructures formed by adhesion ofthe different single components via seed-mediated method. The hybrid nanomaterials have great poten-tials for real applications in many other fields. The nanohybrids have been used as efficient heterocatalystsfor carbon monoxide conversion and photodegradation of organic contaminants. The enhanced catalyticactivity of these hybrid nanocatalysts could be attributed the formation of oxygen vacancies and electrontransfer across the structural junction in a hybrid system as a result of the interfacial particle–particleinteractions. The synergistic combination of up-converting and semiconducting properties in an up-converting semiconducting hybrid particle results in appearance of sub-band-gap photoconductivity.This behavior has a great significance for the design of photovoltaic devices for effective solar energy con-
version. The functionalization and subsequent bioconjugation of the hybrid nanostructures to afford themultifunctional nanomedical platforms for simultaneous diagnosis and therapy are reviewed. The conju-gated multifunctional hybrid nanostructures exhibit high biocompatibility and highly selective bindingwith functional groups-fabricated alive organs through delivering them to the tumor sites. The clevercombinations of multifunctional features and antibody conjugation within these vehicles make them togenerally offer new opportunities for clinical diagnostics and therapeutics.
Colloidal hybrid nanostructures have attracted particularesearch attention because of their unique shape- and composition-ependent properties [1,2]. Thus, bringing together componentsf intrinsically different functionality constitutes a particularlyowerful route to creating novel multifunctional materials withynergetic properties found in neither of the constituents. Cou-ling of two or more components produces a hybrid nanostructurehat allows electronic transfer across the junction to change locallectronic structure [1,3]. The chemical reactivity on the particleurface is thus dependent on the internal and external interfacingapabilities and the particle size distribution of the deposited parti-les on the nanosupports [4]. These featured properties make them
o generally have potential applications in catalysis, optical device,olar energy conversion, chemical sensor, and biomedical detection
method for targeted drug delivery, bioimaging, cancer diagnostics,which would go beyond those of the individual components [3,5,6].
One of the most exciting aspects of the nanomaterials is thedevelopment of the effective approach for the synthesis of thehybrid nanostructures. Significant advances in the controlled syn-thesis of the hybrid nanostructures have been made in recent years[1,7–9]. The synthesis of the hybrid nanoparticles requires the com-bination of two or more dissimilar materials onto one system.The synergetic properties of the multicomponent nanostructuresare dependent on the morphology, elemental composition, andfunctional surface, that is relative to the interface area and activesite density. This subjective is able to achieve by manipulat-ing reaction chemistry of seed-to-precursor ratio, heterogeneousnucleation-growth kinetics, and nature of coordinated organic link-ers. The seed-mediated growth methods have been developedfor the synthesis of the hybrid nanostructures that are typicallyformed by sequential growth of the second components on the
preformed seeds through directed attachment. A combinationof synthetic control along with understanding of the interfacialparticle–particle interactions is therefore a significant basis for theformation of the multifunctional hybrid nanomaterials.
Catalysts based on hybrid nanostructures have attracted consid-rable attention in environmental and atmospheric sciences [10].he hybrid nanostructures have been used as an efficient catalystor chemical conversions. The promotion of the catalytic activity of
hybrid structure is attributed to the interfacial particle–particlenteractions, that is proposed to originate from the contributions:i) presence of active sites, (ii) charge transfer between depositedpecies and nanosupport, (iii) size/shape effects [11]. When usinghe nanohybrids for CO conversion, the particle–particle interac-ions occurred in a hybrid particle could facilitate the formationnd migration of oxygen vacancies to enhance the oxygen stor-ge capability of nanosupports. The adsorbed CO molecules onhe active sites would react with oxygen extracting from theupport surface leaving oxygen vacancy to convert intermedi-te carbonate species and finally its decomposition to CO2 [12].hile the metal/semiconductor hybrid nanocatalysts used for
hotocatalysis, under irradiated light, the deposited metals act asffective sinks for transferring electron from the semiconductorurface to the reagents to perform the oxidation/redox processes13].
An another important opportunity for the hybrid nanostruc-ures pertains to their use in solar energy conversion. The globalonsumption of fossil fuels gradually rises year after year, resultingn exhaustible natural resources and environmentally hazardousombustion in the future. Finding out efficient energy resourcelternatives is questionable as is one of the best solutions. The studyn the development of new materials for increasing the conver-ion efficiency has become an essential part of materials science.he use of photovoltaic cells to convert directly “green” sunlightnto electricity makes them promising candidates for this objective.olid-state materials comprised of organic polymer and semi-onductor species are currently designed in photovoltaic devices14,15]. It is now well understood that the hybrid nanostructuresoupled semiconductor quantum dots with lanthanide-doped up-onverting nanocrystals were considered as a novel material toeet the on-board energy demands. These up-converting semi-
onducting hybrid materials exhibited a high energy conversionfficiency as a result of appearance of sub-band-gap photoconduc-ivity and acceleration of charge separation process [16].
Several types of the plasmonic–magnetic anduorescent–magnetic hybrid nanostructures are potentiallyseful for biomedical applications [17,18]. For example, theuorescent–magnetic materials would be very interesting asual-use biological tags, giving the ability to visualize labeledells using both magnetic resonance and fluorescence imagingechniques, while external magnetic fields could be employedor the directed assembly of such materials [19]. In order to beompatible with biomedical environment, the surfaces of thenorganic nanohybrids are functionalized with appropriate silica,mphiphilic polymer, targeting ligand through chemisorption,ovalent linkage, and ligand exchange [20]. After surface modi-cation, the coated hybrid nanoparticles become high colloidaltability in aqueous media compatible with further bioconjugation21]. The delivery of the hybrid nanoparticles to targeted cellss one of the most obstacle in medical diagnosis and therapy.evelopment of the biomolecule-conjugated strategy allows
he hybrid nanoparticles delivering to targeted tissues throughntibody–antigen or ligand–receptor interactions [20]. The biocon-ugation of the water-soluble nanohybrids is therefore essentialor cellular targeting, achieving by either adsorption or chemicalonjugation of biomolecules to the functionalized surface of theybrid nanoparticles. The biomolecule-conjugated nanohybrid
olloids with promising multifunctional properties could becomeighly selective binding with alive organ, making them to bebiocompatible” behavior and superior bioactivity for smart drugelivery vehicles, MRI contrast agents, and diagnostic devices [22].
iointerfaces 103 (2013) 326– 344 327
The recently significant progress made in the design, fabrication,and various practical applications of the diverse hybrid nanostruc-tures was exhaustively summarized in this review. Structure ofthe review has six sections. First is introduction to the hybridnanostructures followed by the synthetic method mentioned thedifferent routes through heterogeneous growth. The structural-controlled nanohybrids are mainly dependent on the syntheticparameters including the nature of crystal structure, seed-to-precursor ratio, and organic linkers in the surfactant-assistedsynthesis. Catalytic performance and energy conversion of thehybrid nanomaterials, arising from the particle–particle interac-tions are mentioned in the corresponding third and fourth sections.Next, two approaches of coating of silica and amphiphilic polymeron the hybrid surface accompanied by the recent experimentalefforts were reviewed. Finally, the conjugation of biomoleculeswith the functionalized hybrid nanostructures and the use of themas multimodal bioprobes for multimodal imaging and therapy arehighlighted.
2. Synthesis of hybrid nanostructures
Wet-chemically seed-mediated growth provides an effectivemethod for the synthesis of the hybrid nanoparticles with well-controlled structures, where the secondary species attach andsequentially grow on the preformed seeds. To ensure the depositedspecies well-dispersed on the supports, heterogeneous nucleationand growth through atomic addition must be achieved and homo-geneous nucleation should be avoided. Significant progress hasbeen achieved in the synthesis of the core–shell and dumbbellnanoparticles combining two different components. When theindividual components involved have similar crystal structuresand lattice parameters, each component fuses together giving thedumbbell shape. In a dumbbell structure consisted of one particle-bounded another, charged transfer across nanoscale junction couldsignificantly change local electronic configuration that give theremarkable properties. While large lattice space difference of theindividual components results in the core–shell-shaped structureobtained by growing a uniform layer of a shell material around col-loidal particles. An isolation of core from surroundings could createthe specific materials with emerged properties to those of the barenanoparticles [23,24].
The colloidal nanohybrids are generated upon reaction ofmolecular precursors in the liquid solution in the presence ofsurfactants. Once the synthesis is activated at a suitable tem-perature, monomers are generated, and then induced nucleationof nanoparticles and sustain their subsequent enlargement. Theorganic surfactants play key roles along the courses of the hybridformation. Fig. 1 shows general growth models for the fabricationof the dumbbell- and core–shell-shaped hybrid nanostructures,that can be classified into the synthetic routes: (i) the directheterogeneous growth of the secondary precursors on the sitesor tips of the preformed seeds (Fig. 1a–c); (ii) the metal clus-ters adsorbed on the opposite-charged surface of the supportsby photo-irradiation (Fig. 1d); (iii) the reduced precipitation ofthe secondary precursors adsorbed on the hydrophilic-surfacednanohybrids through ion-exchange deposition (Fig. 1e); (iv) thesecondary precursor growth on the support surface after chemi-cal activation of their surface (Fig. 1f); (v) the one-pot growth ofthe secondary precursors on the supports through self-assembledcontrol (Fig. 1g). Following these pathways, a large variety ofthe nanohybrids including metal–metal, metal–oxide, oxide–oxide,
metal–semiconductor structures has been synthesized succes-sively.
Plasmonic–magnetic nanohybrids provide a promising plat-form for developing the optical and magnetic multifunctional
328 T.-D. Nguyen / Colloids and Surfaces B: B
Fig. 1. A general sketch of the reaction mechanisms for the formation of thehybrid nanostructures: (a–c) heterogeneous nucleation and growth of the sec-ondary precursors on the preformed seeds; (d) secondary precursors adsorbed onthe opposite-charged surfaced supports by photo-irradiation; (e) reduced precipita-tion of the secondary precursors on the hydrophilic-surfaced supports; (f) secondarypn
prSviwaoomoaitobpe
disordered networks of the fused hybrid nanostructures. The selec-
recursor growth on the activated-surfaced supports; (g) “One-pot” self-controlleducleation-growth.
robes for cell imaging applications. Materials researchers haveecently been efforted to synthesize the hybrid nanostructures.hevchenko et al. [26] synthesized the gold-iron oxide core–shellsia thermolysis of Fe(CO)5 at the surface of the gold nanoparticlesn octadecene/oleylamine/oleic acid. These hybrid nanostructures
ere formed by deposition of an iron shell around the gold corend subsequent oxidation of the metallic iron shell to form an ironxide hollow through Kirkendall effect. The heterogeneous growthf the iron precursors on the gold seeds was dependent on theolar ratio of oleylamine/oleic acid capping agents. The thinnest
xide shell (∼2 nm) surrounded the gold nanoparticles was formedt oleylamine/oleic acid ratio of 1:1. The irregular polycrystallineron oxide shells connected with the gold core were formed inhe presence of oleylamine without oleic acid. With increasing theleic acid concentration led to the iron nucleation and growth to
e slowed because of the formation of the stable iron oleate com-lex in high-temperature reaction. The gold-iron oxide core–shellsxhibited the surface plasmon resonance shift of the gold particles
iointerfaces 103 (2013) 326– 344
and the magnetic hysteresis loop shift of the iron oxide particles,originating from the core–shells with particle–particle interac-tions. Choi et al. [25] synthesized the metal/oxide core–shellsthrough thermolysis of the mixtures of transition metal–oleate(Fe, Mn) complexes and metal–oleylamine (Au, Ag, Pt, Ni) com-plexes in oleylamine/octadecene. These complexes were preparedfrom transfer-phase reaction of the inexpensive metal salts andsurfactants. Fig. 2 shows the simple and general method for the syn-thesis of the hybrid nanoparticles of Au–Fe3O4, Ni–Fe3O4, Au–MnO,Pt–Fe3O4 with core–shell sphere, flower, snowman shapes. Dueto the high solubility of the prepared complex precursors in1-octadecene solvent, this method was able to large-scale synthe-sis of the well-shaped nanohybrids per a singe preparation. TheAu–Fe3O4 particles became soluble in water by encapsulating theirsurface with a PEG-phospholipid shell. The amino-functionalizedAu–Fe3O4 nanohybrids conjugated with thiolated oligonucleotidesequences exhibited the red shift of the surface plasmon reso-nance of the gold particles and the enhanced signal intensity of theFe3O4 particles in T2-weighted magnetic resonance imaging. Theseconjugated hybrid nanostructures have potential in multimodalbiomedical probes.
The other plasmonic–magnetic hybrid materials of the Au-Cocore–shells and Au-Ni spindly nanostructures were synthesized byWang and Li [27] through one-pot solvothermal reaction of HAuCl4and metal nitrate (Co(NO3)2·6H2O or Ni(NO3)2·6H2O) in octadecy-lamine used as both solvent and surfactant. The formation of thesehybrid structures was illustrated by the metal-induced reductionprocess namely, the octadecylamine-supplied electron cloud sur-rounded Au atoms reduced the transition metal ions to form thenanohybrids. The strong magnetism of these plasmonic–magneticnanohybrids and the CO superior catalytic activity of the Au-Cocore–shells were showed as a result of incorporating magneticheterometals into gold particles. The authors also expressed thatthe cysteine-linked Fe3O4 nanoparticles were carried out by for-mation of amide bonds between surface amino groups of theFe3O4 nanoparticles and carboxylic groups of cysteine [28]. Thebifunctional Au–Fe3O4 nanohybrids prepared from conjugationof the Au particles to the thiol-modified Fe3O4 nanoparticles bystrong interaction between Au and thiol group under ultrasonicconditions. Lysine contained both amino and carboxylic groupsplayed dual roles as both linker and capping agent in attachingmetals on the Fe2O3 particles. The hybrid nanostructures can beused for magnetic separation of biosubstances and for proteinseparation.
Plasmonic–semiconductor hybrid nanostructures have seen arenewed interest in photocatalytic degradation of organic con-taminants and photocatalytic water splitting [30]. Banin’s groupsynthesized various classes of these materials via photodeposi-tion of metals on semiconductors [1,31]. The Au@CdSe/CdS hybridnanorods were synthesized through growing Au precursors on onlythe reactive facets exposed tips of the seeded rods [32]. UnderUV excitation, the large Au domains were exclusively deposited atone end of the seeded CdSe/CdS rod because of electron migra-tion to one of the reactive facets of the tips. The strong Au-Secoordination allowed the Au precursors at high concentration togrow further on the side facets of the seeds. The Au-CdSe pyra-mids were obtained by growth and reductive transformation ofa gold shell around a CdSe pyramid under electron beam irradi-ation. The deposition of the gold clusters along the anisotropicsemiconductors was strongly influenced by reaction temperatureand ligand-mediated defect sites. Decreasing the amount of sur-factant allowed the gold tips to interact and coalesce, forming
tive growth of the gold precursors on the tips of the CdSe rod,tetrapod, pyramid exhibited a significant modification of the opti-cal property compared to the corresponding singe components.
Fig. 2. Synthesis and bioconjugation of metal-oxide hybrid nanostructures. (a) A synthetic procedure of oligonucleotide-conjugated metal-oxide hybrid nanostructures; (b)the detection of conjugated nanohybrids toward complementary oligonucleotides; TEM images of various hybrid nanostructures synthesized from thermolysis of mixedmetal–oleate and metal–oleylamine complexes in octadecene: (c) Au–Fe3O4, (d) Ni–Fe3O4, (e) Au–MnO, (f) Pt–Fe3O4.
eproduced with permission from Ref. [25]. 2008 American Chemical Society.
he authors also hypothesize that a redox reaction may be takinglace in which gold cations are being reduced as, in this instance,elenium anions are being oxidized. The authors also synthesizedhe cage-shaped Ru/Cu2S nanohybrids by adding Ru(acac)3 to Cu2Seed suspension in octadecylamine [33]. The metallic Ru selec-ively grew on the crystal edges of the Cu2S nanocages to form
symmetrical cage around a Cu2S core. The cage formation coulde due to the capping of thiol ligands on the facets of the Cu2Sarticles as a result of blocking the growth of these crystal facets.hese Ru/Cu2S nanocages were used as an excellent electrocatalystor H2O2 sensing with catalytic activity higher than the bare Cu2Slectrode.
There are reports on the magnetic–semiconductor nanohy-rids with unique physiochemical properties. Deka et al. [29]eported the two-step seeded-growth for the selective synthe-is of the Co-tipped CdSe/CdS core–shell nanorods. Fig. 3 showshe two-step procedure consisted of injection of the tri-n-octylhosphine sulphide/CdSe seeds to the Cd-surfactant complexes
nd heated at 350–380 ◦C to form the CdSe/CdS core–shells. Theo clusters were then attached with the CdSe/CdS seeds by
njecting the Co2(CO)8 solution into octadecene solvent contain-ng CdSe/CdS seeds at 200–240 ◦C under inert atmosphere. An
excess volume of oleic acid was added to the growing mixtureto stabilize the hybrid nanostructures formed after reaction com-pletion. The formation of the nanohybrids with matchstick-liketopology was predicted by crystal-oriented-attachment occurredthe directional fusion of the generated Co nanocrystals to thenanorod tips. These Co-tipped CdSe/CdS heterostructures exhib-ited unusual room-temperature ferromagnetism and fluorescentemission despite photoexcited charge transfer from the semicon-ductor to the metal domain. Lee et al. [34] synthesized the FePt/PbSand FePt/PbSe nanohybrids with magneto-transport properties bycoupling the ferromagnetic FePt particles with either PbS or PbSein form of core–shells or dumbbells. Fig. 4 shows the forma-tion of the hybrid products by injecting bis(trimethylsilyl) sulfideto the reaction mixture containing FePt nanoparticles, oleic acid,Pb-oleate complex dissolved in octadecene at 120–150 ◦C. Thenanohybrid shape was controlled by capping of the ligand on thesurface of the FePt seeds and the reaction temperature. Thesemagnet-in-the-semiconductor hybrid nanostructures showed the
semiconductor-type transport properties with magnetoresistancecharacteristic of combining the advantages of both functionalcomponents. The maghemite-metal sulphide (ZnS, CdS, HgS)nanohybrids were synthesized by adding sulfur and appropriate
Fig. 3. Synthesis of ferromagnetic-fluorescent Co-tipped CdSe/CdS core–shell nanorod hybrids. (a) Preparation of CdSe/CdS nanorods from CdSe; (b) Co-tipped CdSe/CdScore–shell nanorods formed by thermolysis of Co2(CO)8 in the octadecene containing CdSe/CdS nanorods; (c) energy-filtered TEM (EFTEM) image and (d) correspondingcomposite false-color chemical map upon EFTEM superimposition of bare CdSe/CdS nanorods and of matchstick-like Co-tipped CdSe/CdS nanorods.
eproduced with permission from Ref. [29]. 2009 American Chemical Society.
etallorganic precursors to the Fe2O3 particles followed by heat-ng treatment [35]. In other reports, the large lattice mismatch
etween Fe2O3 and metal sulphide resulted in the formation of theon-centrosymmetric nanostructures. The formations of trimersnd oligomers were observed for ZnS and dimers for CdS and HgS
ig. 4. Synthesis of magnet-in-semiconductor FePt–PbS and FePt–PbSe hybrid nanostrucEM images of the FePt–PbS nanohybrids with (b) dumbbell and (c) cubic core–shell morpRTEM images with 5 nm scale bars.
eproduced with permission from Ref. [34]. 2010 American Chemical Society.
nanocomposites. The alloy-cadmium selenide core–shells includ-ing FePt/CdSe, NiPt/CdSe, FePt/CdSe, NiPt/CdSe were synthesized
by hydrolysis of cadmium stearate in oleylamine, hexadecy-lamine/octyl ether, 1,2-hexadecandiol in the presence of alloyseeds [36].
tures. (a) Morphology directing synthetic conditions for the FePt–PbS nanohybrids;hologies; (d) TEM image of dumbbell-like FePt–PbSe nanohybrids. The insets show
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T.-D. Nguyen / Colloids and Surface
. Nanocatalysis
.1. Carbon monoxide conversion
The low-temperature oxidation of carbon monoxide is one ofhe current important environmental issues, since small expo-ure (ppm) to this odorless invisible gas can be lethal. Automobileollution is also one of the factors contributing to global warm-
ng. One solution for reducing pollution is to lower the operatingemperature of the catalysts for the purification of gas pollutants.ybrid nanostructures have widely used for heterogeneous cataly-
is for low-temperature carbon monoxide (CO) conversion [37]. Theetal/oxide nanohybrids often exhibit an enhanced catalytic activ-
ty arising from the particle–particle interactions [38]. Differentspects have thus been studied in order to explain such extraordi-ary catalytic behavior, including the nature of metal active sites,
nfluence of support, synthetic method, and pre-treated catalysts.The interest in the oxide-supported Au catalysts has increased
ubstantially since Haruta et al. [40] discovered that the smallu nanoparticles are exceptionally active for low-temperature COxidation. The exploration of the catalytic performance of the Auanoparticles on the basis of the sizes has been the main focus ofost researches in this field. The later studies were also reported
y the authors that the isolated gold particles decorating the differ-nt oxide supports (TiO2, �-Fe2O3, Co3O4) achieved 50% conversiono CO2 and O2 at temperatures as low as −25 and 10 ◦C, respec-ively, with CO turnover rate increasing dramatically when the
etal crystals were ≤4 nm in diameter [41]. While the nature ofctive sites for CO oxidation on supported Au catalysts is still beinglucidated, increasingly gained experimental evidence continueso show that the interaction at the metal–oxide contact boundariesan be properly tuned by systematically reducing the particle sizef the support oxides.
Cerium oxides have been used as a support for three-way cat-lyst (TWC) and other catalyst applications because of their redoxeaction of releasing and storing oxygen under low oxygen par-ial pressures. The interfacial interactions of the deposited metalarticles could lead to change the electronic state of the ceriaupports that accelerates the formation of surface oxygen vacan-ies for catalytic oxidation process. Glaspell et al. [42] reportedhe enhancement of the CO catalytic activity at low tempera-ure directly correlated with the change in the morphology of theupports and the dispersed deposition of the small-sized metalAu, Pd) particles. Guzman et al. [43] found that the CO catalyticctivity of the Au nanoparticles was dramatically enhanced withepositing on the ceria nanorods caused the prevention of theold clusters from the agglomeration. Andreeva et al. [44] sug-ested that the high activity of the gold/ceria catalysts causeshe enhanced electron transfer between defective ceria and par-ially charged gold through oxygen vacancies. Mrabet et al. [45]eported the modified two-phase method for the synthesis of thelkyl chain-capped metal (Cu, Au) particles and oxide nanoparti-les (TiO2 and ZrO2) followed by their cooperative assemblage intohe metal/oxide nanohybrid mesostructures. These metal/metal-xide hybrid materials exhibited high surface areas, narrow poreize distributions, and exceptional catalytic properties in CO con-ersion, even surpassing the performance of the commercial nobleetal catalysts. Most of the enhanced catalytic activities of the
eria-supported gold catalysts were discovered likely due to theigh oxygen storage capacity of ceria supports. The oxygen vacan-ies were then assumed to adsorb on the ceria nanoparticles,here it may or may not dissociate before reacting with CO
olecules adsorbed on the gold nanoparticles. Fig. 5 shows the
emperature-dependent evolution of the CO conversion over theu/Fe3O4 catalysts prepared by thermolysis of iron precursorsn gold seeds in comparison with the conventional catalysts.
iointerfaces 103 (2013) 326– 344 331
The dumbbell-shaped Au/Fe3O4 nanohybrids exhibited a half-conversion temperature of −25 ◦C compared to a value of 30 ◦C forthe conventional Au/Fe2O3, while the temperature was 67 ◦C forthe Pt/Fe3O4 nanodumbbells and about 100 ◦C for the conventionalPt/Fe2O3. The enhanced catalytic activity was not only strongerelectronic interaction and larger hetero-junction interface, but alsodue to thermal stability of the hybrid catalysts against sintering[39].
The incorporation of either two species of deposited agentor of support together also offer the improvement of the cat-alytic activity of the nanohybrid systems. Abdelsayed et al.[46] demonstrated that the bimetallic alloys-decorated ceriananohybrids prepared by microwave irradiation methodshowed the CO catalytic activity according to the orderCuPd > CuRh > AuPd > AuRh > PtRh > PdRh > AuPt. The catalyticimprovement was a result of alloying bimetallic species. Yuanet al. [47] prepared the mesoporous CeO2-Al2O3 by incorporating8 mol% ceria particles with the size of 3–4 nm into the orderedmesoporous alumina and used them as a mesoporous support fordecorating the 7 nm-sized Au particles. The 8 wt.% Au/mesoporousCe-Al oxide catalysts exhibited the excellent catalytic activitywith 100% conversion occurring at 26 ◦C, which was much betterthan 1 wt.% Au/mesoporous Al2O3 and 1 wt.% Au/CeO2 catalysts.This was attributed to the nature of the mesosupports and thegold–ceria interaction in determining the Au catalysts’ activity.
3.2. Photocatalysis
Environmental water problem has recently provided the impe-tus for sustained fundamental and applied research in the area ofenvironmental remediation. About 0.7 million tons of dyes usedwith the demand for textile colorants, food additives, paints, cos-metics are produced annually worldwide [48]. It has been reportedthat approximately 10–15% of the dyes are lost during manufac-turing processes, [49,50] resulting in a seriously environmentalproblem. Therefore, the decolorization and degradation of organicdyes before release to the environment are important. Photo-catalysis with semiconductor-based particles has been studiedextensively because of its potential in environmental applicationsof photodegradation of organic contaminants and hydrogen gener-ation by water splitting [51].
In single semiconductor (e.g., TiO2) photocatalysts, photogen-erated electrons (e−) and holes (h+) migrate to the particle surface,where they act as redox sources, ultimately leading to the destruc-tion of pollutants [52]. In most instances, the valence band holesand conduction band electrons simply recombine competitivelyliberating heat or light, a process known as mutual recombination.Because the recombination is expected to occur on grain bound-aries and crystalline defects, the use of single-crystalline particleswith a low density of defects is one of the possible strategies.Indeed, single-crystalline anatase particles usually exhibit a highlevel of photocatalytic activity when they have nanoscale parti-cles and large specific surface area, providing more active catalyticsites. However, because of its large band-gap (3.2 eV), TiO2 mainlyabsorbs ultraviolet light, giving rise to a very low-energy efficiencyin utilizing solar light. Therefore, new photocatalysts activatedunder visible-light irradiation have been exploited extensively.
From this viewpoint, developing TiO2-based photocatalystswith wide-band-gap electronic structure operated under visible-light irradiation is indispensable because these materials have ahigh catalytic efficiency, low cost and are environmentally sus-tainable. Two approaches have been considered to modify the
electronic structure of the titania namely, (i) coupling of the metalparticles with the titania and (ii) doping nonmetal atoms (e.g.,nitrogen) into the lattice of the titania [52]. Interparticle trans-fer of charge carriers contributes to the enhanced photocatalytic
Fig. 5. Dumbbell-like metal-oxide nanohybrids for CO catalytic conversion. HRTEM images of (a) Au–Fe3O4, (b) Ag–Fe3O4, and (c) AuAg–Fe3O4 nanohybrids; (d) CO conversionl cataly
ight-off curves of Au–Fe3O4 and Pt–Fe3O4 nanohybrids and commercial Au-Fe2O3
eproduced with permission from Ref. [39]. 2010 American Chemical Society.
fficiency of the coupled semiconductors when the energies ofalence and conduction bands are properly matched. In this section,e concentrated on coupling of two nanocomponents. Combina-
ion of the metal part with large surface area facilitates chargeeparation for photocatalysis. Following visible-light absorption,he rapid charge separation takes place at metal–semiconductornterface to induce the separated charges for redox performance.lectrochemical experiments illustrated the role of the depositedetal particles as a mediating site in storing and shuttling pho-
ogenerated electrons from the semiconductor to an acceptor inhotocatalytic process. The remarkable photocatalytic activity ofhe metal/semiconductor nanohybrids has been reported in recentear.
The photocatalytic activity relative to the band structure of aybrid system was presented in Ag/ZnO heterojunction as a typicaloncept [53]. In the Ag/ZnO system, due to the chemical potential ofnO (5.2 eV) larger than that of Ag (4.26 eV), electrons migrate fromg to the conduction band (CB) of ZnO through Ag–ZnO interaction
o achieve the Fermi level equilibration. When the hybrid catalystsre illuminated by UV light with photon energy higher than theand-gap of ZnO, electrons (e−) in the valence band (VB) can bexcited to the CB with simultaneous generation of the same amountf holes (h+) left behind. The deflexed energy band in the spaceharge region facilitates the rapid transfer of the excited electronsrom ZnO to Ag particles, which increases the lifetime of the pho-ogenerated pairs. Electrons accumulated at the Ag particles or theD of ZnO can be transferred to oxygen molecules adsorbed on theurface to form free oxygen radicals, such as
•O2
−,•HO2,
•OH, and so
orth, while the photo-induced holes react with surface-bound H2Or OH− to produce the hydroxyl radical specimens (
•OH), which
s an extremely strong oxidant for the mineralization of organichemicals.
sts.
Fig. 6 shows a scheme for electron–hole separations, energyband matching, and photocatalysis of the Ag2O/TiO2 heterostruc-ture synthesized using coprecipitation process [54]. The authorsrevealed that the deposition of the Ag particles on the TiO2supports can improve its photocatalytic efficiency through theschottky barrier conduction band electron trapping and consequentlonger electron–hole pair lifetimes. Under visible-light irrada-tion, the visible-light photocatalytic activity of the Ag2O/TiO2heterostructures, TiO2 nanobelts, Ag2O nanoparticles was testedby photocatalytic degradation of methyl organe aqueous solu-tion. Within 24 min, the degradation was only 9% for TiO2 belts,74% for Ag2O nanoparticles, and 80% for Ag2O/TiO2 hybrids.The improvement of the hybrid catalysts may be attributedto heterostructure effect of coordination junctions, which caneffectively suppress the hole–electron recombination rate underUV light irradiation. It has been widely accepted that the Ptdeposited on the titania particles can suppress the recombina-tion of electron–hole pairs in TiO2, where the Pt particles actas electron traps aiding electron–hole separation. The Pt/TiO2nanowire hybrids with 5 nm Pt particles well-dispersed on thesurface of the TiO2 nanowires were fabricated by hydrothermaland reduction process [55]. The Pt–TiO2 hybrids served as aneffective photocatalyst because the small sized-Pt incoporationon the TiO2 surface can accelerate the electron–hole separationand the charge transfer to dissolved oxygen molecules. The influ-ence of the Pt loading values on photocatalytic efficiency wasfound. The 1 at.% Pt-TiO2 nanocatalysts exhibited the highest pho-tocatalytic activity on methylene blue degradation. However, the
high Pt loading value did not mean a high photocatalytic activ-ity. Higher content loaded Pt nanoparticles can absorb moreincident photons which did not contribute to the photocatalyticefficiency.
Fig. 6. Ag2O/TiO2 nanobelt hybrids with enhanced ultraviolet and visible photocatalytic activity. A schematic view for electron–hole separation and energy band matching ofthe Ag2O/TiO2 hybrid nanostructure under (a) ultraviolet and (b) visible-light irradiation; (c) TEM image of Ag2O/TiO2 nanobelts; (d) degradation of methyl orange catalyzedby Ag2O, TiO2 nanobelts, Ag2O/TiO2 nanobelt hybrids under ultraviolet light irradiation.
eproduced with permission from Ref. [54]. 2010 American Chemical Society.
The synthesis and design of the ZnO/TiO2 nanocomposites wereynthesized to improve the quantum efficiency of the photocata-ysts for water purification applications [56]. This is due to theigh reactivity of TiO2 and the large binding energy of ZnO, which
mprove the process of electron and hole transfer between theorresponding conduction and valence bands. The ZnO tetrapodsoated with the TiO2 particles were also suggested for high photo-atalytic efficiency. The ZnO/TiO2 composite nanotubes were usedor the evaluation of the effective photocatalytic degradation ofumic acid. The Fe3O4/SiO2/TiO2 core–shells with enhanced pho-ocatalytic activity were synthesized by combining two steps of theol–gel process with calcination [57]. The control over the size andrystallinity of the TiO2 supports made possible the improvementigher photocatalytic efficiency compared to Degussa P25. The pho-ocatalytic efficiency of the TiO2 nanocrystal shell increased in theresence of SiO2 interlayer which helped the chemical and thermaltability of the Fe3O4 core.
We recently studied the synthesis of colloidal hybrid nanocrys-als and represent the state of the art in the nanomaterials research.he hybrid nanostructures combined multicomponents exhibitedollected properties as a result of the interfacial interactions. Weave developed the novel approaches for the controlled synthe-is of the metal/oxide nanohybrids. Namely, the metal particlesere coupled with the nanosupports using seed-mediated growth
n assistance of bifunctional organic linker [58], photodeposition59], and ionic exchange techniques [60]. The resulting nanohybridse.g., metal/TiO2) showed the enhanced photocatalytic perform-nces compared to the bare catalysts [58,60].
. Hybrid nanostructures for energy conversion
The rising global consumption of fossil fuels causes a gradualxhaustion of our natural resources and contributes to the climatehange [61]. Among the green energies, solar power is one of theost sustainable energies due to its abundance and renewability
and photovoltaic cells (PV) have been used as efficient device toconvert the sunlight into electricity [62]. Quantum dots and tita-nia semiconductor nanoparticles have often used as light absorbersand electron acceptors in solution-processed polymer solar cells todate [63,64]. However, regardless the specific material used, theefficiency of all single-junction PV devices is limited by the fact thatall photons with energy below the semiconductor’s band-gap arenot converted, and all photons with energy higher than the band-gap loose part of their energy (get “thermolyzed”). These materialspossess the large band-gap leading to their rapid charge carrierrecombination and low charge separation process. The band-gapsof their single semiconductors lie in the ultraviolet regime whichis only a small fraction of the sun’s energy. Thus in order to effi-ciently use sunlight as energy source, its absorbable light must beextended to the visible region.
Semiconductors have a filled band preferred to the “valenceband” and an empty band known as the “conduction band”. Whenthe scale of a semiconductor is down to several nanometres result-ing in a strong quantum size effect [65]. Up-conversion (UC) refersto nonlinear optical processes, in which the sequential absorp-tion of two or more photons via intermediate long-lived energystates leads to the emission of light at shorter wavelength than theexcitation wavelength. Lanthanide-doped up-converting nanopar-ticles are a key luminescent material in optoelectronical fieldsdue to their ability to convert low-energy near-infrared (NIR)photons to visible light [66]. It is well known that inorganic nanohy-brids containing two or more components emerge new synergisticproperties [67]. One effective approach to achieve this goal iscoupling of semiconductor quantum dots with lanthanide-dopedup-converting nanoparticles.
As a specific example to clarify this proof-of-concept, Yan
et al. [16] recently studied the energy transfer from up-converter(lanthanide material) to energy acceptor (semiconductor). Fig. 7shows the synthesized hybrid nanostructures consisted of theEr/Yb-doped NaYF4 nanoparticles decorated with the CdSe
Fig. 7. Near-IR photoresponse in up-converting CdSe/NaYF4:Yb,Er hybrid nanostructures. (a) TEM image of CdSe/NaYF4:Yb,Er (CSNY) nanohybrids; (b) photographs of theemission from NaYF4:Yb,Er nanoparticles (top) and CSNY nanohybrids (bottom); (c) I–V characteristics of the CSNY-based device in the dark (black line) and under 980 nmradiation (red line), the bottom inset shows the dependence of the photocurrent on the laser power; (d) on–off switching characteristics.(For interpretation of the referencesto color in this figure legend, the reader is referred to the web version of the article.)
uantum dots. In a semiconductor/lanthanide-doped up-onverting nanostructure system, the dopant as luminescententers (exciton) and the host lattice as a matrix to bring thesexcitons into semiconductor acceptors at interface. These novelybrid nanomaterials could work through up-conversion of the
ow-energy near-infrared (NIR) light by lanthanide materials, thenduced excition is being transferred to semiconductor species
here it dissociates generating mobile charges. This synergisticombination allows to appear sub-band-gap photoconductivitynd accelerates charge separation process in a semiconductingp-converting nanohybrid. This behavior can effectively absorbunlight for increasing energy conversion efficiency. The two-ontact devices are prepared by spin-coating of solution of studiedanoparticles in toluene on Si/SiO2 substrates pre-patterned withu electrodes, which is aimed to study its photoconductivity.he authors found that hydrazine-cross-linked films of theseanoheterostructures showed pronounced photoconductivityhen excited with NIR laser. The materials exhibited the improvedroperty compared to using silica shell to attach CdSe to the
anthanide nanocrystals that precludes electronic interactionetween the CdSe and renders its semiconducting properties
he other hybrid systems for photovoltaics have also been exploredy different researchers. For example, the ZnO-CdSSe core–shellanoarrays were synthesized with controlled composition and
hell thickness by chemical vapor deposition on the ZnO nanowirerrays [68]. The experimental results revealed that the depositednO shell grew along the [0 0 0 1] wire axis of the wurtzite ZnO core.he (0 0 2) fringes were separated by a constant distance which was
close to that of the bulk. This approach was also applied to fabri-cate the high-quality TiO2-CdS and ZnO25CdS0.5Se0.5 core–shells.The successful synthesis of the ZnO- or TiO2-based photoelectro-chemical cells would be a key step toward the construction ofthe novel viable nanometer-scale solar cell devices. The electronicstructures of the CdSe/CdS core–shell nanorods were systemicallyinvestigated by large-scale first-principles quality calculations [69].The effects of band alignment, quantum confinement, piezoelectricfield, dipole moments were analyzed and delineated by comparingthe results of systems with or without some of these attributes. Theauthors found the complicated interplays between these effects inband in determining the nanorod gap and electron hole wave func-tion localizations. The hole wave function was found to be localizedinside the CdSe core, while the electron wave function was local-ized in the CdS shell, with its distance to the CdSe core depending onthe surface passivation. The permanent dipole moment induced bydifferent surface passivations could change the electron hole sepa-ration, while the piezoelectric effect played a relatively minor role.The PbSe/CdSe/CdS nanohybrids with two distinct geometries ofcore–shells and tetrapods were synthesized by sequential additionof small amounts of cadmium oleate and elemental sulfur dissolvedin octadecene to the PbSe/CdSe nanoparticles at 240 ◦C [70]. In com-bining efficient emission in the IR with exceptionally long excitonlifetimes, these novel hybrid nanostructures exhibit extremely longcarrier decay times up to 20 �s. The increase in carrier lifetimesis attributed to the reduction of the electron–hole overlap as a
result of delocalization of the electron wave function into the outerCdS shell or arms. The ultralong carrier lifetimes of these materi-als could offer opportunities for useful applications from lasing tophotovoltaics.
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. Functionalization of hybrid nanostructures
Functionalization of the hybrid nanostructures has received great deal of interest because of their biomedical applicationsn targeted drug delivery, diagnosis and therapy. The synthe-is of the hybrid nanomaterials has mostly been achieved inrganic and aqueous media containing either hydrophobic orydrophilic organic linkers. The hybrid nanostructures synthesizedsually involves organic linkers binding to the surface of two orore components to stabilize the nuclei and larger nanoparti-
les against aggregation by repulsive force for controlled growthf the sized and shaped nanohybrids. As capped by the linkers,he resulting hybrid nanostructures become hydrophobic characternd is insoluble in water, resulting in incompatible with biolog-cal systems. A surface modification of the hydrophobic-surfacedanohybrids to produce water-soluble functional nanohybrids isherefore an indispensable step prior to biomedical applications.hese interactions with the environment ultimately affect the col-oidal stability of the particles and may yield to the delivery ofppropriate functional nanoparticles to targeted species. There areommon functionalization strategies of silica and amphiphilic poly-er coatings. Since the coated hybrid nanostructures retained their
riginal physical properties, the resulting nanocomposites showedhe multifunctional properties. These routes can serve as a pow-rful paradigm for the further fabrication of antibody-conjugatedanohybrids for multifunctional theranostic applications.
.1. Silica coating
Coating of a cross-linked silica shell to protect therganic agent-capped hybrid cores from external environ-ent is carried out to produce the silica-coated hydrophobic
anohybrids. Coating with silica layer is one of the mostidely used methods for surface modification of the inorganicanoparticles, because the unique properties of the nanoparticlesan be preserved by silica shells. After silica coating, the colloidstabilized in aqueous media and have low nonspecific interactionith biosystems and inert silica layer against degradation of
ptical properties. Silica can also be easily surface modified to linkioconjugators with interesting biofunctionalities. To this goal,tober sol–gel and water-to-oil microemulsion methods haveenerally been achieved for silica coating.
The Stober method of base-catalyzed hydrolysis and conden-ation of tetraethyl orthosilicate (TEOS) to produce silica used tooat on the hybrid cores [71]. This reaction has several advan-ages such as mild conditions, low cost, without surfactant used.arlier, Rogach et al. [72] coated the hydrophilic CdTe quan-um dots within 40–80 nm silica spheres using modified Stober
ethod, which resulted in reduced emission intensity with broad-ning of the spectrum. The quantum dots acted as seeds forhe silica growth in ethanol/water. This method yielded singler multiple quantum dot per silica sphere, but the size andispersion of the silica-coated quantum dots were hard to con-rol. Gerion et al. [73] achieved Stober silanization approachor the functionalization of mercapto-silane/(3-mercaptopropyl-rimethoxysilane) siloxane with thiol and/or amine groups toroduce the silica-shell-coated hydrophobic CdSe/ZnS core–shells.he mercaptopropyltris(methyloxy)silane (MPS) was replaced theOPO molecules on the surface. The methoxysilane groups (Si-CH3) of (MPS) hydrolyzed into silanol groups (Si-OH), and formed
primary polymerization layer. The silane precursors contain-ng functional groups (F = –SH, –NH2) were then incorporated into
he shell and may tailor the nanoparticle surface functionality.dopting the Stober method, the seminal silica coating of theitrate-reduced Au particles by Liz-Marzán et al. [74] involveshe weak surface attachment with bifunctional (3-aminopropyl)
iointerfaces 103 (2013) 326– 344 335
trimethoxysilane in aqueous media. The –NH2 groups were boundto the gold surface and –Si(OEt)3 groups and facilitated forhydrolysis and condensation with sodium silicate to deposit asurface-coated silica layer. Later, the thicker silica shells can begrown on the surface-stabilized Au particles by further hydroly-sis/condensation of tetraethyl orthosilicate (TEOS).
In some cases prior to silica coating, the particle surface shouldbe attached with hydrophilic molecules to create the surface-protected nanoparticles stabilized in aqueous media. This couldfacilitate hydrolysis/condensation of tetraethyl orthosilicate. Forexample, Liu and Han [75] synthesized the monodisperse silica-coated gold particles derived from the citrate-stabilized goldparticles. The prepared citrate-reduced gold particles are low sta-ble for silica coating in alcoholic media. The colloidal stabilityneeds to be increased by introducing a certain amount of sodiumcitrate into the synthetic solution to replace the surface chargeof the gold particles. Hsu et al. [76] presented the synthesis ofthe silica nanohybrids composed of the CuInS2/ZnS quantum dotsand magnetite nanocrystals. The outside silica-shell grafted withpoly(ethyleneglycol) and amine groups to provide better biocom-patibility and to allow further bioconjugation. These materialsexhibited the exert excellent properties for drug delivery vehiclesand magnetic resonance imaging. The conjugation of Pt(IV) anti-cancer drug onto the nanohybrids resulted in higher cytotoxicitythan the free Pt(IV) anticancer drug, indicative of the multifunc-tional feature of the synthesized nanohybrids.
One successful example involved the surface adsorption ofmethoxypoly(ethylene glycol) silane to replace oleylamine cappedon the silver nanoparticles by Shen et al. [77] which is subject tofurther hydrolysis/polycondensation to form the thin silica layer-stabilized silver nanoparticles followed by thick silica coating withthe Stober process. The bifunctional Gd2O(CO3)2·H2O/silica/Auhybrid nanoparticles prepared by condensation of TEOS followedby conjugation with the gold shells were demonstrated potential asa MRI and therapeutic agent [78]. The hybrid particles showed thecapability of absorbing NIR radiation for photothermal destructionof cancer tumors, in which the Au shell thickness strongly influ-enced the NIR optical absorption and photothermal effect. Sotiriouet al. [79] achieved coating of a thin silica shell on the Ag/Fe2O3Janus-shaped hybrids via one-step flame aerosol method. The silicacoating still intacted their shape and plasmonic–magnetic proper-ties but minimizes the release of toxic Ag+ ions from the Ag particlesurface and their direct contact with live cells. The well-definedhybrid Au/SiO2/CdSe nanostructures constituted a gold core over-coated with a silica shell followed by a dense monolayer of theCdSe quantum dots were formed via multistep procedure [80]. Theformed products involved the synthesis of the gold particles, goldsurface activation, silica-shell deposition, modification of the silicasurfaces with –NH2 groups, and final self-assembly of CdSe quan-tum dots onto the particle surfaces. In order to the surface activationof the gold particles, (3-mercaptopropyl)-trimethoxysilane wasfound to be better than (3-aminopropyl)-trimethoxysilane becauseof stronger binding of –SH groups to the gold surfaces. These hybridstructures were used to perform the accurate quantitative analysisof the effect of the metal on quantum dot photoluminescence inten-sity. Khlebtsov et al. [81] preformed the silica coating on the Au–Agnanocages through adding water–ammonia solution and TEOS tothe reaction solution containing Au–Ag particles. The silica-coatedAu–Ag nanocages were then functionalized with the photody-namic sensitizer Yb-2,4-dimethoxyhematoporphyrin to form thenanocomposites potential in the multifunctional capability ofIR-luminescence detection, photosensitization, and photothermol-
ysis.
Reverse microemulsion is a promising method for the syn-thesis of the monodisperse silica-coated nanoparticles [83]. Yiet al. [82] developed the reverse microemulsion-mediated route to
336 T.-D. Nguyen / Colloids and Surfaces B: B
Fig. 8. Silica-coated magnetic-quantum dot hybrid nanoparticles. (a) A schemeof the reverse microemulsion system for the synthesis of silica-coated magnetic-quantum dot nanohybrids; (b) TEM image of the silica-coated magnetic-quantumdot nanohybrids.
water had the same optical spectra and quantum yield as
2005 American Chemical Society.
ncapsulate the hydrophobic trioctylphosphine oxide (TOPO)-apped quantum dots and magnetic particles within silica shellso form the silica-coated quantum dot-magnetic hybrid structures.ig. 8 describes the water-in-oil (W/O) reverse microemulsion sys-em for silica coating of the hydrophobic particles, where waterroplets are stabilized by non-ionic Igepal surfactant in a continu-us oil phase (e.g., cyclohexane). After the addition of silane (TEOS),ydrolysis and condensation occur at W/O interface or in waterhase to encapsulate the inorganic particles within a silica shell.he magnetic particles and quantum dots were confined in the silicaayer to afford the hybrid structure. The silica-coated magnetic-uantum dot nanohybrids preserved the magnetic property of-Fe2O3 and optical property of CdSe quantum dots. The authorslso used this route to synthesize the silica-coated oleylamine-oated Au and Ag core–shells and subsequent conjugation withhe activated polymeric dextran [84]. The resulting materials wereotentially used as glycobiological probes. Similarly, the SiO2-
oated Fe2O3 rattle-type nanoball structures were also synthesizednd used as support for decorating the Pd nanoclusters onto theupport surface by mercapto- or amino-functionalized silica [85].
iointerfaces 103 (2013) 326– 344
The reverse microemulsion process was also used by otherresearch groups. Koole et al. [86] elucidated the mechanism ofincorporating the hydrophobic quantum dots into monodispersesilica spheres. In water-in-oil reverse microemulsion system, thehydrolyzed TEOS had a high affinity for the quantum dot sur-face for replacement of the hydrophobic amine ligands, whichenabled the transfer of the quantum dots to the hydrophilic inte-rior of the micelles where silica growth occurred. Tartaj and Serna[87] achieved in situ synthesis and further silica coating of the Fenanoparticles in microemulsion system. The lamellar-like coatednanostructures were formed through the subtle interplay control-ling the formation of nanospherical silica particles by the ammoniabase-catalyzed hydrolysis of tetraethoxysilane (TEOS) in water-in-oil. Li et al. [88] designed the reverse microemulsion based on theIgepal CO-520 surfactant to produce the silica-coated NiPt nanohy-brids prepared from the reduction of nickel acetylacetionate andplatinum acetylacetonate in oleic acid/oleylamine. Yu et al. [89]reported that the templated sol–gel encapsulation of the CTAB-stabilized micelles containing metal precursors with ultra-thinporous silica coating allows solvent extraction of organic basedstabilizer from the silica-coated Ag–Pt alloys. The water-in-oilmicroemulsion for silica coating on the Y3Al5O12:Ce nanoparticleswas presented by Nien et al. [90] through hydrolysis of tetraethylorthosilicate. The silica-shell thickness can be turned from 8 to16 nm by varying the ratio of NiPt particles to TEOS precursor.
5.2. Amphiphilic polymer coating
Coating a layer of amphiphilic polymers onto the hydrophobicligand molecules-capped nanohybrids could afford the water-soluble particles. Facile adsorption of the amphiphilic polymerson the hybrid surface is typically based on hydrophobic inter-action of hydrocarbon chains and van der Waals force betweenthe molecules. Because of long length of the polymer chains, con-tact points between organic linkers and polymer arise preventingdesorption of the polymer molecules from the particles. Advan-tage of this approach is mainly not dependent on the types of theinorganic hybrid cores and the organic linkers, and the physio-chemical surface properties of the coated particles are significantlyunchanged. A popular example is the gold particles in aqueousmedia prepared by citrate reduction. Citrate ions adsorbed on thegold surface resulted in their negative charge and colloidal stabil-ity within several years by electrostatic repulsion. The citrate layerwas replaced by stronger-binding ligands of mercaptocarboxylicacids. The surface modification of the particles with mercaptocar-boxylic acids allowed for achieving concentrated particle solutions,that can precipitate out of particles by salt-induced aggregation andredissolved in low-salt buffers [91].
The surface functionalization of the TOP/TOPO-capped CdSe/ZnSquantum dots was substituted phosphine-based hydrophobic lig-ands with hydrophilic mercaptocarboxylic acid molecules [92]. Thequantum dots in aqueous solution stabilized with mercaptoaceticacid were modified by co-adsorption of polyethylene glycol andpeptides. A part of the lipids coated on the quantum dots can bindwith amino groups or polyethylene glycol for further functionality[93]. Fig. 9 shows the modular design toward the synthesis of theamphiphilic polymer of poly(maleic anhydride-alt-1-octadecene)(PMAO)–polyethylene glycol through reaction between maleicanhydride and primary amine-terminated polyethylene glycolmethyl ethers and subsequent coating of PMAO–polyethyleneglycol amphiphilic polymer with hydrophobic ligand-cappedquantum dots [94]. The functionalized materials dissolved in
those pre-synthesized quantum dots. The water-soluble encap-sulated nanoparticles contain free carboxylic acid groups forconjugating anti-Her2 antibody to the polyethylene glycol-coated
Fig. 9. Forming biocompatible and nonaggregated nanocrystals in water using amphiphilic polymers. Top: one-step formation of poly(maleic anhydride-alt-1-octadecene)(PMAO)–polyethylene glycol (PEG) amphiphilic polymers through reaction between maleic anhydride and amino groups. Bottom: schematic structure of water-solublequantum dots (F stands for a functional group instead of –OCH3, such as –OH, –COOH, –NH2). Quantum dots were encapsulated by PMAO–PEG amphiphilic polymerhydrophobic interaction.
eproduced with permission from Ref. [94]. 2007 American Chemical Society.
anoparticles. The antibody-conjugated quantum dots were useds a probe to recognize human breast cancer cells with Her2eceptor with nonspecific binding of polyethylene glycol with celleceptors on the particle surface.
Poly(acrylic acid)-based polymers with hydrophobic side chainsere usually used for surface modification with aliphatic amine- or
hiol-capped particles [95]. These polymers are soluble in organicolvent and can bind to the hydrophobic particle surface. Afterolvent evaporation, the particle solids can be dissolved in aque-us buffer, providing stable water-soluble particles. For example,oly(acrylic acid) was coated onto the hydrophobic dodecylamine-apped CdTe/CdSe quantum dots to form the amphiphilicouble-layered nanohybrids soluble in either water or organicedia [96]. The coating of these polymers can carry out in ethanol
olvent, resulting of poly(acrylic acid) backbone linked with mixedctylamine and isopropylamine, giving numerous hydroxyl groups
n the particle surface [97,98]. The hydrophobic side chains ofhe polymers commonly cover or intercalate the hydrophobicigand molecules, and the exposed hydrophilic backbone out-
ards to aqueous media. In addition, poly(maleic anhydride)
copolymers prepared from copolymerization of maleic anhy-dride with olefin are used as alternating copolymers. In aqueousmedia, the maleic anhydride rings hydrolyze and open givingtwo carboxylic groups, which gives access to further function-alization. Each maleic anhydride ring yields a free carboxylicgroup, indicating that the surface of the polymer-coated parti-cles could be covalently grafted to amino acids for biomoleculeconjugation.
Poly(vinyl pyrilidone) was also used to graft directly on thesurface of the particles through one-pot process [96]. The furthersurface functionalization of the grafted products can be achievedby adding a next layer or exchanging original capping agents. Otherpolymers contained a mixture of aliphatic side chains and otherswith primary amines at their ends can bind to the nanoparticle sur-face through the amino groups [99]. Additionally, poly(acrylic acid)modified with free thiol and amino groups at the ends of the side
chains was demonstrated as coating for quantum dots to form a thinshell with little effect on the quantum yield of the coated particles.The hydrophobic–hydrophilic block-copolymers formed in micel-lar structure dispersible in solvent were also used for the coating of
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he nanoparticles. The coating by block-copolymer micelles yieldshe particle aggregates instead of the monodisperse particles thatould be suitable for further generation of the multifunctionalorous materials.
Polyethylene glycol (PEG) is a linear polymer consisted ofthylene oxide units and well soluble in water. PEG is high bio-ompatibility due to its inertness and non-toxic properties [100].EG uses as non-ionic surfactant and as an additive in cosmet-cs, pharmaceuticals and food. PEG-modified proteins showedhe enhanced water solubility in organisms and antibodies bindo a much lesser extent to protein [101]. Apart from the post-
odification approach by covalent chemistry, the PEG-modifiedanoparticles can be obtained by PEG-contained ligand moleculesith functional group that can bind to the particle surface [102].
he particle synthesis can be carried out in the presence of these lig-nds; PEG can be introduced by place-exchange reactions that wereodified with PEG before used for further coating process. Owing
o the solubility of PEG itself, the PEG-coated particles can alsoe dispersed in polar organic solvents [103]. An increasing graft-
ng density and molecular weight of the employed PEG moleculesielded thicker shells that can be found to be of the order of aew to tens of nanometers [104]. Susumu et al. [102] developed aew class of water-soluble ligands consisting of dihydrolipoic acidDHLA) and PEG. The appended functional groups (hydroxyl, car-oxylic acid, amino, biotin) are able to conjugate with biomolecules.he quantum dots capped with DHLA–PEG–biotin interacted withtreptavidin coupled to proteins, which were subsequently takenp by live cells.
. Applications in biomedical diagnosis and therapy
.1. Nanotechnology in cancer treatment
Cancer is an emerging human disease in all over the world. Its a result of unregulated cell division leading to the uncontrolledrowth and spread of abnormal cells. This behavior causes the for-ation of malignant tumors consisted of cancer cells plus some
ealthy cells (normal tissue) invade nearby parts of the body. Atarly growth stages, the cancer cells mostly do not look or act likehe normal cells because they are readily disguised by the healthyells on their surface. This mainly behaves an extremely danger ofhe cancer cells. Tumor cells have a strong tendency to displaceealthy cells until the tumor reaches a diffusion-limited maximalize, frequently resulting of changes to the DNA (mutations), lead-ng to deaths. In further danger of one’s life, the cancer cells caneave the original area and travel to other parts of the body, conse-uently this secondary tumor is referred to as metastasis.
Traditional cancer diagnosis and treatment modalities basi-ally include post-surgical chemotherapy, radiotherapy, hormoneherapy, and immunotherapy [105]. Each of these modalities hasonstantly limitations in treatment and also contributes to the ris-ng costs of healthcare. Because of most human cancers (>85%)elevant to solid tumors, so that the current cancer therapies aresually achieved some surgeries for removal of tumors, followedy chemotherapy and radiotherapy to kill the remaining tumorells (noted post-surgical chemotherapy). However the efficacy ofhe chemotherapy, serious side-effects on different healthy organs,he increased costs are a great obstruction by the fact that can-er stem cells be still survive and could continue to spread back.t is reasonably why cancer symptoms come back within relativehort duration in patients who has passed through the post-surgicalhemotherapy.
Thermal therapies (hyperthermia) have often employed a vari-ty of heat sources including laser light, focused ultrasound,icrowaves to destroy the solid tumors [106]. The benefits of
yperthermia are minimally or non-invasive, relatively simple to
iointerfaces 103 (2013) 326– 344
perform in the absence of surgical resection. However, simpleheating techniques have trouble discriminating between tumorsand surrounding healthy tissues, and often heat intervening tis-sue between source and target site. To irradiating beams reachedunderlying tumors or dispersed into large tumors, high activatingenergy source must achieve at long duration of time, leading tosufficiently penetrate and damage healthy tissues.
To the goal of the cost and performance, the developmentof new efficient approaches based on an advanced combinationbetween “smart drug delivery” chemotherapy and photoradiationcompanied by “near-infrared (NIR) laser-adsorbing nanomateri-als” to create the most effective results have been interested inmedicine technology [107]. Lack of target specificity is one of themajor disadvantages of many drugs. When drugs administered intohuman body are distributed to all organs through bloodstream,rather than to specific target organ that needs the pharmacolog-ical treatment. Biochemical and physiological barriers of certainorgans also limit drug delivery to the desired organ. Chemothera-peutic drugs may destroy the cancer cells along with destroy thehealthy tissue and cytotoxic effect of the drugs. To overcome thesedisadvantages, newer and effective methods should be developedto safely shepherd a pharmacological agent to avoid specific organs,where healthy tissue might be adversely affected.
Nanoparticles that are 100–10,000 times smaller than thecells can easily pass through the cell membrane and accu-mulate into target sites by manipulation. Due to their largesurface areas, the nanoparticles can be readily conjugated withmolecular moieties capable of recognizing various complemen-tary biomolecules including DNA strands and antigens with highsensitivity and selectivity, which is advantageous in targetedimaging, diagnosis, and delivery [22]. This nanometer dimen-sion becomes even more important when the nanoparticles aresystemically administered into living organisms. The functional-ization of the silica-coated nanohybrids is usually achieved byadsorption or chemical conjugation of the biomolecules to theparticle surface. The stable silica-coated gold-based nanohybridcolloids can be surface-functionalized with mercapto-, amino-,carboxy-terminated silanes for bioconjugation. Biomolecules suchas small molecules (vitamins, peptides, lipids, sugars) and largerones (proteins, DNA, antibodies, enzymes, chitosan) are often usedto conjugate onto the silica-coated particles. The homogeneouslywater-dissolved biomolecules-conjugated silica-coated nanoparti-cles could bind to the surface of the cancer cells with greater affinitythan to the noncancerous cells.
The targeted delivery of the gold-based nanohybrids to solidtumors is one of the most important and challenging problems incancer medicine. The strong plasmon absorption and photother-mal conversion of the gold nanoparticles were exploited in cancertherapy through the selective localized photothermal heating ofcancer tumors [108]. To treat a tumor, the gold particles conju-gated with biomolecules can be selectively targeted to cancer cellswithout significant binding to healthy cells. The nanoparticles inthe bloodstream generally have to firstly move across the tumorblood vessels. The tumors are then exposed to an excitation source,such as NIR laser light, radiowave, or an alternating magnetic field.When the gold nanoparticles are exposed to the light radiation attheir resonance wavelength, the electric field of light causes the col-lective oscillation of the conduction band electrons at the particle
surface. The coherent oscillation of the metal free electrons in reso-nance with the electro-magnetic field is called the surface plasmonresonance (SPR). The excitation of the maximum SPR absorptionresults in enhancement of the photophysical properties of gold
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articles [109]. As a result, the gold nanoparticles absorb the inci-ent energy and convert it into heat, which raises the temperature∼42 ◦C) of the tissue and ablates the cancerous cells by disruptinghe cell membrane. The photoradiations do not often kill healthyells because the laser power requires to heat/destroy the cancerells much low than the healthy cells to which nanoparticles do notind specifically. The physical heating mechanism of ablative ther-pies would provide an advantage against chemotherapy-resistantancers, as well as improved tumor response when combined withhemotherapy and photoradiation.
Key features to consider when selecting a compatible particle foryperthermia are the wavelength of maximal absorption, absorp-ion cross-section, and shape/size of the particle. NIR laser lights ideal for in vivo hyperthermia applications because of its lowbsorption by tissue chromophores (hemoglobin and water), whichrevents them from damaging healthy tissue. The absorption coef-cient of these tissue chromophores is as much as two orders ofagnitude greater in the visible region (400–600 nm) as compared
o the NIR region (650–900 nm) [109]. Gold nanoparticle-mediatedhotothermal therapy is predominantly designed to operate inhis window of wavelengths (“NIR window”) to minimize energynteraction of light-tissue, preventing damaging heating of healthyissue. Upon tumor laser irradiation, NIR light is absorbed byhe nanoparticles and heat dissipation is generated as a con-equence of electron–phonon interactions. For successful cancerblation, the tissue must be heated to a minimum temper-ture for a minimum duration of time to induce tumor celleath.
The plasmon absorbance of the gold particles can be easily tunedrom the visible region into the NIR by simple manipulation of theirspect ratio (from sphere to rod) [109]. For the gold nanospheres,his resonance occurs in the visible spectral region at about 520 nm,riginating from the brilliant color of the gold particle solution.wing to their distinctive rod shape, the gold nanorods have twobsorption peaks attributed to the free electron oscillation alonghe longitudinal and transverse axis, resulting in a stronger reso-ance band in the NIR region and a weaker band in the visible region∼520 nm for gold nanospheres). The synthesis of the colloidal goldanorods would therefore prove effectively for photothermal ther-py because they can absorb low-energy NIR light and convert it toeat in the usual way.
The gold species conjugated to antibodies can be selectively tar-eted to cancer cells without significant binding to healthy cells. Ineneral, the routes to nanoparticle delivery are mainly based on anactive” mechanism and a “passive” mechanism [110]. In the activeode, the molecule ligands of antibodies, DNA, and peptides are
sed to recognize specific receptors on the tumor cell surface. Inhe passive mode, the nanoparticles without targeting ligands areccumulated and retained in the tumor interstitial space mainly.n both mechanisms, the nanoparticles in the bloodstream mustrst move across the tumor blood vessels. Some reports were usedEG ligand to attach the lysine-capped Au nanoparticles throughysine-terminated PEG link [111]. The targeted delivery of the goldanoparticles to solid tumors is one of the most important and chal-
enging problems in cancer nanomedicine. It was recently observedhat the colloidal gold nanoparticles were found in dispersed andggregated forms within the cell cytoplasm and provided anatomicabeling information. The anti-EGFR antibody-conjugated nanopar-icles homogeneously bind to the surface of the cancer type cellsith greater affinity than to the noncancerous cells. These resultsere detected by using SPR scattering imaging and SPR absorption
pectroscopy, in which a relatively sharper SPR absorption band
ith a red shifted maximum compared to that observed on non-
ancerous cells [112]. We recently reviewed the aqueous-basedynthetic pathways of the metal nanocrystals potential in biomed-cal applications [110].
iointerfaces 103 (2013) 326– 344 339
6.3. Hybrid nanostructures in simultaneous diagnosis andtherapy
Clever combinations of different types of the functional nano-structured materials enable the development of multifunctionalnanomedical platforms for multimodal imaging or simultaneousdiagnosis and therapy. Types of the hybrid nanostructures withsynergistic plasmonic–magnetic; fluorescent–magnetic propertiesare ideal platforms for constructing multifunctional materials. Thebinding of the hybrid nanoparticles to biological molecules has cre-ated a rapidly expanding field of research for achieving this goal.
6.3.1. Plasmonic–magnetic hybrid nanostructuresMagnetic nanoparticles exhibited unique magnetic property is a
direct consequence of the behavior of electrons within the particle.The electrons are similar to tiny bar magnets, with a surround-ing magnetic field that corresponds to the electron spin in anapplied field. When electrons move between different energy lev-els, they absorb energy and can generate light or heat [21]. Becauseof their low toxicity and good sensitivity, the magnetic particlesconjugated with biomolecules are widely studied and applied inbiomedicine, where these particles used as magnetic carriers thattravel to targeted cancer tumors under orientation of external mag-netic field. The magnetic carriers then absorb externally magneticalenergy and convert them into heat to kill the cancer cells. Magneticresonance imaging (MRI) is presently one of the most powerfuldiagnosis tools for imaging the central nervous system and fordetecting tumors and cancer cells. The paramagnetic gadoliniumchelate complexes (e.g., Gd-DTPA) have been widely used for MRIcontrast agents [113]. The porous/hollow iron oxide nanocapsulesmade by wrap-bake-peel process from FeOOH nanorods via silicacoating were used for this goal [114].
A combination of the plasmonic particles and magnetic par-ticles generates the plasmonic–magnetic nanohybrids that retainplasmonic feature and strong response to magnetic fields, wherescattering of the plasmon alongside with magnetic contrast couldbe envisioned. Recently, many researchers have developed the newclass of the plasmonic–magnetic nanohybrids to further improvethe contrasting abilities with extra functions. As a typical materialfor cancer diagnostics and therapeutics, the Au/Fe3O4 nanohybridsas a bifunctional probe offer two functional surfaces for attachmentof plasmonic and magnetic particles [115]. The Au and Fe3O4 par-ticles both in a hybrid system are known to be highly compatiblewith biomedicine and a consequence of extending for diagnosticsand therapeutics. The Au and Fe3O4 interfaces result in drasticallychange the local electronic structure, leading to an enhancementof their synergistic properties. The plasmonic and magnetic prop-erties of the nanohybrids could be optimized by adjusting the sizeof the two particles. In comparison with the single Au and Fe3O4particles, the Au/Fe3O4 hybrids possessing simultaneous plasmonicand magnetic detection facilitate for cancer diagnosis and ther-apy. When the biomolecules-conjugated Au/Fe3O4 hybrids aredispersed in body, they could travel to the targeted cancer tumorsby influence of external magnetic field. The Au and Fe3O4 particlesin the hybrid system adsorb energy from irradiating laser light andfrom exposing external magnetic field, respectively, and convertthem into heat to kill the cancer cells. By using these bifunctionalmaterials, an abundant amount of synergistic heating within thecancer tumors is created by a simultaneous adsorption-conversionof Au and Fe3O4 species facilitating the heating of the cancer cells.
Sun’s group, as a well-known research group in nanohybrids-applied nanomedicine, has developed the effective approaches to
synthesize the biomolecule-conjugated hybrid nanostructures forstudying MRI contrast agents [116]. The authors were carried outthe thermolysis of Fe(CO)5 on the surface of the Au nanopar-ticles in octadecene to produce the Au–Fe3O4 dumbbells that
Fig. 10. Fluorescent–magnetic–biotargeting multifunctional nanobioprobes for detecting and isolating multiple types of tumor cells. (a) Schematic drawing of the avidin-coupled fluorescent–magnetic nanohybrids. Fluorescent–magnetic nanohybrids were covalently coupled with avidin and then coated with biotinylated goat anti-mouse IgGvia the biotin–avidin interaction. Mouse monoclonal antibody (mAb) was then attached to the nanohybrids via the binding to the goat antibody; (b) fluorescence microscopicimages of anti-CD3 mAb-coupled red nanobioprobes; (c) anti-prostate-specific membrane antigen mAb-coupled yellow nanobioprobes.(For interpretation of the referencest .)
o color in this figure legend, the reader is referred to the web version of the article
eproduced with permission from Ref. [121]. 2011 American Chemical Society.
ere then coupled with Herceptinand platin complex [117]. Theisplatin complex was linked to the Au surface by reacting Au--CH2CH2N(CH2COOH)2 with cisplatin. The coating of Herceptinntibody on the Fe3O4 particles was performed by PEG3000-CONH-erceptin. The cisplatin–Au-Fe3O4–Herceptin nanohybrids were
ested to HER2-positive breast cancer cells and HER2-negativereast cancer cells. The cisplatin–Au–Fe3O4–Herceptin hybridsevealed the high efficiency in the killing of HER2-positive cancerells. The presence of the hollow inside the nanohybrids was wit-essed as an efficient carrier for targeted delivery and controlledelease of cisplatin. These materials illustrated the possibility of act-ng as multifunctional platform for target-specific platin delivery.esides, the other plasmon-magnetic materials of FePt/Fe2O3 yolk-hells [118] and mesoporous silica-coated Au–Fe3O4 core–shells119] were also synthesized and extensively studied for strong MRIontrast agent enhancement and carriers for anticancer drug deliv-ry.
.3.2. Fluorescent–magnetic hybrid nanostructuresThe magnetic nanoparticles are widely employed as MRI
ontrast agent, while the quantum dots have already emergeds a powerful new family of biological fluorescent tags. Byombining both the fluorescent–magnetic functionalities in oneybrid nanoparticle that have been used as biolabeling andontrast agents, and for magnetic resonance imaging (MRI),eading recently to major advances in cancer cell and tumormaging.
In comparison with conventional organic dyes and fluores-ent proteins, the quantum dots have unique optoelectronic
roperties with size-tunable light emission, superior signal bright-ess, resistance to photobleaching, and broad absorption spectra
or simultaneous excitation of multiple fluorescence colors. Inrder to establish the utility of the quantum dots for biological
sensing application, the quantum dots are injected into the desiredcells of animals (e.g., mouse), emitted green and red labels arespectrally resolved to the eye clearly under the excitation of asingle light source by a laser scanning microscope. For exam-ple, Chen et al. [120] used the synthesized triantennary dendriticgalactoside-capped ZnS/CdSe nanohybrids as a hydrophilic, fluo-rescent, multivalent probe for detecting the metastatic lung cancercells. The water-soluble nanohybrids were selectively uptaken bylung cancer cells enriched with membrane-bound asialoproteinreceptors. The results suggested the stronger interaction betweenpolyhydroxylended nanohybrids in the membrane compositionand cancer cells.
Nevertheless, the use of the single semiconductor quantum dotsfor biosensor application still has some limitations. Namely, thequantum dots are frequently emitted at UV and visible regions,meanwhite the biological samples (water and tissues) also induceautofluorescence by the absorption of ultraviolet and visible light,possibly leading to an inexact diagnosis. Moreover, if the biologicalsamples are prolonged exposure to UV radiation, it would causethe photo-damage and mutation. Therefore, the use of the quan-tum dots emitted in the near-infrared spectrum is an alternativeapproach for the imaging of tumor structures in vivo. The fluo-rescent emission peaks of these desired nanoparticles are in thelow-energy NIR (800–1000 nm), distant from the typical UV–visspectrum (400–600 nm) of tissue autofluorescence. This uniquefeature of the near-infrared quantum dots makes probes easilyrecognisable under near-infrared light, even in the tissues with highfluorescent background.
To overcome this barrier, one novel approach is based on
conjugation of two components in a fluorescent particle sys-tem. The fluorescent emission peaks of the quantum dots couldbe shifted from ultraviolet to near-infrared region, arising fromparticle to particle interface. It is noted that the iron oxide
ssisted by externally applied magnetic field; (c) tumor location as defined by MUC
eproduced with permission from Ref. [123]. 2011 American Chemical Society.
anoparticles exhibit specific magnetic property. Because theuantum dots did not show the magnetism, consequently, theuantum dots coupled with superparamagnetic particles couldrovide the two-in-one multimodal fluorescent–magnetic nanohy-rids, which could act as multi-targeting, multifunctional andulti-treating tools. As a specific example, the bifunctionalagnetic–fluorescent nanoprobe allows for a preoperative diag-
osis via MRI owing to the fluorescent–magnetic properties. Theylly the high sensitivity and resolution of the fluorescence phe-omenon to the high spatial resolution and noninvasiveness of MRI.urthermore, the interaction between quantum dots and magneticarticles could result in NIR fluorescent emission of the nanohy-rids.
Visual sorting and manipulation of tumor cells through usinguorescent–magnetic–biotargeting multifunctional nanobio-robes were reported by Song et al. [121]. The avidin-conjugateduorescent CdSe/ZnS-magnetic �-Fe2O3 nanohybrids synthesizedere used to perform detection and extraction of multiple types
f cancer cell targets via high affinity between antigens and
ntibodies. Fig. 10 presents the synthetic procedure for theseaterials. The single particles of CdSe/ZnS and �-Fe2O3 were
oupled together in the chloroform/butanol suspension contain-ng hydrazine-treated poly-(styrene/acrylamide) copolymer. The
intensity increases within magnetic field treatment for 1 h.
avidin-coupled fluorescent–magnetic multifunctional nanohybridswere then obtained by incubating aldehyde-containing avidinwith fluorescent–magnetic bifunctional nanohybrids. The authorsdemonstrated that the avidin-coupled fluorescent–magneticmultifunctional nanobioprobes detected and extracted twodifferent types of tumor cells (leukemia cells and prostate can-cer cells) from complex samples containing both normal cellsand the target cancer cells and the capture efficiencies wereof about 96% and 97%, respectively. Upon exposing magnetand fluorescence microscopes, these multifunctional materi-als were very sensitively detect and isolate target tumor cellsat low concentration of 0.01% in the mixed cells. Wang et al.[122] synthesized the fluorescent–magnetic nanospheres byco-embedding quantum dots and magnetite nanoparticlesinto hydrazide-functionalized copolymer nanospheres fol-lowed by coupled on the surface with IgG, avidin and biotinto form the fluorescent–magnetic–biotargeting trifunctionalnanospheres. The nanoscale biocomposites can selectively linkto apoptotic cells, allowing their visualization and isolation.
The fluorescent–magnetic particles were inert with respect tocell proliferation and tumor formation and served as both anegative contrast agent for in vivo MRI, as well as a fluores-cent tumor marker for optical imaging in vivo and in vitro. The
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ultifunctional capability of the nanocomposite nanoparticless MRI and fluorescence imaging probes, along with their poten-ial as drug delivery vehicles, makes them novel candidates forimultaneous cancer diagnosis and therapy.
The surface functionalization of the nanohybrids consistedf a polymer-coated maghemite superparamagnetic core and adSe/ZnS quantum dot shell, with anticycline E antibodies wasermitted the separation of MCF-7 breast cancer cells from serumolution. The surface immobilised anticycline E antibodies boundpecifically to cyclin, a protein which is expressed on the surface ofreast cancer cells. The separated cells were monitored by fluores-ence imaging microscopy, due to the strong luminescence of theseanohybrids [82]. An interesting external magnetic motor effectn floating cells, treated with fluorescent–magnetic nanocompos-tes, has been reported by Yoon et al. [124]. In an another report,he CdS:Mn/ZnS fluorescent–magnetic core–shells were preparedy using water-in-oil microemulsion. The peptide-conjugateduorescent–magnetic core–shells possessing fluorescent, radio-pacity, and paramagnetic properties were used to label andisualize brain tissue without manipulating the blood–brainarrier. The fluorescent visualization of the whole rat brain waschieved using a simple low power handheld UV lamp, indicateshat these materials are potentially applicable for an advanced mul-imodal detection system [125].
One of the main problems in the preparation of theuorescent–magnetic nanohybrids is the risk of quenching of theuorophore on the surface of the particle by the magnetic core.his quenching process could be occurred because of fluorophoreontact with the particle surface, resulting in an energy trans-er process. The problem of quenching can be partially resolvedy coating of a stable shell (e.g., coating of a thin silica layer)n the magnetic nanoparticles prior to the introduction of theuorescent molecules. As a proof-of-concept, Selvan et al. [126]mployed the silanization in a reverse microemulsion to produce ahin silica coating on the bare quantum dots or magnetic particlesith surface NH2 groups. The silanized particles were conjugated
o oleyl-O-poly(ethylene glycol)succinyl-N-hydroxysuccinimidylster through binding of the surface amine groups with hetero-unctional polyethylene glycol. The biocompatible silica-coatedan effectively target the cell membranes of HepG2 humaniver cancer cells, NIH-3T3 mouse fibroblast cells, and 4T1
ouse breast cancer cells. These results demonstrated that theseaterials have potential for drug loading and delivery into cancer
ells to induce cell death.The biological applications of the down-conversion lumines-
ent materials are currently restricted because they frequentlymit at UV and visible regions, given the autofluorescence fromiological tissues. These limitations would be breakthrough if weiscover an alternate materials emitted in near-infrared (NIR)-to-is upconversion [127]. This expectation was proved by Zhang et al.123] who recently developed the new mesoporous multifunc-ional materials based on the combination of both up-convertinguminescent and magnetic properties. As shown in Fig. 11, theanorattle hollow spheres consisted of the rare-earth-doped NaYF4hells with a SiO2-coated Fe3O4 inner particle fabricated throughon-exchange process. The silica coating of the Fe3O4 nanoparticles
ere carried out by hydrolysis of TEOS in reverse microemul-ion system. The Fe3O4@SiO2@Y2O3/Yb,Er magnetic upconversionxide nanospheres were prepared by coating with the layer of/Yb,Er(OH)CO3·H2O via homogeneous precipitation in the aque-us solution of yttrium nitrate and urea and subsequent calcinationt 550 ◦C for 2 h. The Fe3O4@SiO2@�-NaYF4/Yb,Er magnetic upcon-
ersion fluoride nanorattles were formed via ion-exchange ofhe Fe3O4@SiO2@Y2O3/Yb,Er particles in HF and NaF solution. Toemonstrate the material’s potential use as a drug delivery system,he magnetic upconversion fluoride nanorattles were conjugated
iointerfaces 103 (2013) 326– 344
with antitumor drug doxorubicin. Through in vitro experiments inmice cells, the authors demonstrated that the material emits visibleluminescence upon NIR excitation and can be directed by externalmagnetic field to specific target, making it an attractive system fortargeted chemotherapy. This enabled selective fluorescent labeling,imaging and potentially sorting of the cells opening new prospectsin cancer diagnostics and therapy.
7. Conclusion and outlook
This review has shown the various emerging applications inthe broad areas of diverse types of the colloidal hybrid nano-structures synthesized using seed-mediated growth. Throughheterogeneous growth, depending of the structure and geometryof the nanohybrids on the crystal structure of each compo-nent, the nature of organic linkers, the seed-to-precursor ratio insurfactant-assisted synthesis that has been presented is impres-sive. In multicomponent systems, one can expect novel and uniqueproperties that originate from collective interactions between theconstituents. The outstanding understanding of how growth join-ing of two individual materials could allow us to control the finalnanohybrid geometries with desired properties. As these proto-cols show more robust, the hybrid nanostructures prepared bycombined individual features in different geometry arrangementwill provide insight into the bonding, hybridization, and interac-tion of different materials systems at the nanometer scale. Theparticle–particle interactions in the hybrid system could lead togeneration of oxygen vacancies and photo-induced electrons/holeson the support surface which accelerate the heterogeneous cat-alytic process. The development of efficient photoconductivitynanomaterials based on the hybrid nanostructures is a greatchallenge in the fields of nanotechnology. The marriage of anup-converting semiconducting hybrid nanoparticle is a promisingway to combine the up-converting with semiconducting proper-ties resulting in appearance of sub-band-gap photoconductivity.This could open access to a fine control of charge transfer processbetween different components of the heterostructures that applyin photovoltaic cells for effective energy conversion.
A major goal in nanomedicine is the coherent implementationof multifunctional platforms within a single targeted nanodeliv-ery system that would simultaneously perform diagnosis, targeteddelivery and efficient therapy. The hybrid nanomaterials arebecoming a hot research area as they enable the tracking of cells tosimultaneous medical therapy and diagnosis. The synergistic com-binations of the plasmonic–magnetic and fluorescent–magneticfeatures and subsequent functionalization and bioconjugation ofthe colloidal hybrid nanoparticles have created a series of the well-defined hybrid nanostructures that can be integrated to generatethe multifunctional nanocomposite systems, while retaining theirindividual functional characteristics. These hybrid nanostructureswere shown to be viable not only as dual-functional probes forimaging but also as an anticancer drug delivery vehicle even ori-entation of NIR excitation and external magnetic field. Throughin vitro experiments demonstrated that these conjugated hybridnanoparticles were actively delivered and targeted to the tumorsites in alive organs.
It is thus anticipated that the multifunctional nanomaterials willoffer potentially nanotechnological applications toward environ-ment consideration, energy resource, and nanomedicine. In thefuture, the synthesis of various inorganic hybrid materials withhierarchical structures using simple and economical approaches
are needed, and accomplishing this has been very challenging forthe design of advanced hybrid nano devices. Anticipated mile-stones include these multifunctional materials could open newperspectives for broad applications when considering the range
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f material combinations, coherent geometries, and engineeringollective properties. This would significantly contribute to theevelopment of the scientific and applied field to be contiguouso materials science. We expect that this review is a significantlyeport for readerships evaluated systematically in diverse type ofhe hybrid nanomaterials, which will offer new occasions for fur-her potentials in applied science.
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