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Colloids and Surfaces A: Physicochem. Eng. Aspects 290 (2006) 70–76

Combined investigation of experimental characterization and theoreticcalculation on the structure of dextran-Fe3O4 clusters

Ke Tao, Hongjing Dou, Kang Sun ∗The State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200030, PR China

Received 23 January 2006; received in revised form 27 April 2006; accepted 28 April 2006Available online 16 May 2006

bstract

Dextran-Fe3O4 hybrid clusters were fabricated by coprecipitating ferric and ferrous ions in the presence of dextran, and after characterizationf these clusters combined with calculation based on classical nucleation theory, a structure model of these hybrid clusters was proposed. Theybrid cluster was believed including small Fe3O4 nanoparticles and dextran which acted as both nucleating agent and stabilizer, so that exist inoth the inside of magnetite nanoparticles and the periphery of the hybrid clusters. Besides, the effects of WCD (weightiron cation:weightdextran) andolecular weight of dextran on the size, morphology and magnetic property of clusters were also investigated in this paper. It was found that

he variation of WCD and molecular weight of dextran have great effect on the size of the hybrid clusters, but have almost no effect on the sizef the Fe3O4 nanoparticles. The characterization of magnetic property demonstrated that the Fe3O4 nanoparticles are of a single domain and theaturation magnetization was affected by the size of dextran-Fe3O4 hybrid clusters. 2006 Elsevier B.V. All rights reserved.

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eywords: Fe3O4 nanoparticle; Dextran; Hybrid cluster; Copreciptation; Struc

. Introduction

As one of the phases of iron oxide, magnetite (Fe3O4) haseen found numerous applications due to its extraordinary mag-etic property [1]. In addition, nanoscale magnetite exhibits anxcellent magnetic property so that makes it a potential clin-cal reagent applicable to magnetic resonance imaging (MRI)2], hyperthermia [3] and drug delivery [4]. Unfortunately, pureanoscale magnetite would aggregate seriously due to its largeurface energy; consequently, numerous reports have been pub-ished on stabilizing these particles using different stabilizersuch as a surfactant or a macromolecule matrix [5–10]. Amonghese stabilizers, water-soluble macromolecule (WSM) is oneind of important stabilizer because the magnetic nanoparticlestabilized by WSM hold high stability and hydrophilicity, andre potential in biomedical applications for the aqueous envi-

onment in organism [11].

Dextran is one kind of water-soluble polysaccharides whichas been clinically used for more than half a century [12].

∗ Corresponding author. Tel.: +86 21 62932555; fax: +86 21 62830735.E-mail address: ksun@sjtu.edu.cn (K. Sun).

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927-7757/$ – see front matter © 2006 Elsevier B.V. All rights reserved.oi:10.1016/j.colsurfa.2006.04.052

ecently, it has been investigated as potential macromoleculararriers for delivery of drugs and proteins, primarily to increasehe longevity of therapeutic agents in the circulation [13]. Thexcellent biocompatibility makes dextran a good stabilizer ofanoscale magnetite.

Among different approaches to fabricate metal oxideanoparticles, the coprecipitation of cations in aqueous solu-ions is the most convenient and cheapest one [14]. Dextrantabilized magnetite is easily prepared by mixing the solutions ofextran, iron salt and alkali (such as ammonia, sodium hydrox-de, etc.). In fact, the features and physical properties of dextrantabilized magnetite synthesized by coprecipitation have beenesearched by many groups, but few researches investigatedhe effect of molecular weight and dosage of dextran on theesultant dextran-Fe3O4 clusters. It is normally recognized thathe dextran-Fe3O4 nanoparticles synthesized by this methodomposed with a Fe3O4 core and dextran existed mainly onhe periphery of the nanoparticles to stabilize the hydrophobice3O4 core (as shown in Scheme 1A) [15,16].

In this paper, we synthesized dextran stabilized magnetiteanoparticles by the coprecipitation method, and investigatedhe effects of WCD (weightiron cation:weightdextran) and molec-lar weight of dextran on the size, morphology and magnetic

K. Tao et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 290 (2006) 70–76 71

S in mos e3O4

ptnm

2

2

ftSkprc

2

o

F

IFUadttgaufs

ibcdpw

2

Mpcwesatuheating rate under nitrogen atmosphere. The crystallite phaseof dextran-Fe3O4 clusters was identified by recording X-raydiffraction patterns (XRD) using a D8 Advance Diffractome-ter (Bruker, Germany) equipped with a Cu K� radiation source.

Table 1Weight and molecular weight of dextran used in experiment

Sample no. WCD (weightiron cation:weightdextran) Molecular weightof dextran (k)

20A 1:2.5 2020B 1:5 2020C 1:7.5 2020D 1:10 20

cheme 1. Scheme of the structure model and formation mechanism proposedtructure proposed in most references, and B: the structure model of Dextran-F

roperty of dextran-Fe3O4 clusters. A new structure model ofhese clusters was proposed based on the classical theory ofucleation of particles and the experimental results. Besides,agnetic property of dextran-Fe3O4 clusters was investigated.

. Experimental

.1. Materials

Analytical grade ferric chloride hexahydrate (FeCl3·6H2O),errous chloride tetrahydrate (FeCl2·4H2O), ammonia solu-ion(25% wt) and dextran (Mw ≈ 20000) were purchased fromhanghai Sinopharm Chemical Reagent Co. Ltd. Other twoinds of dextran (Mw ≈ 40000 and Mw ≈ 60000–90000) wereurchased from Fluka. All these reagents were used directly aseceived. Milli-Q water was used in the synthesis of nanoparti-les, and de-ionized water was used in the rinsing of clusters.

.2. Preparation of dextran/Fe3O4 hybrid clusters

The dextran/Fe3O4 nanoparticles were precipitated in a non-xidizing environment according to the chemical reaction:

e2+ + 2Fe3+ + 8OH− → Fe3O4 + 4H2O

n a typical procedure, 0.005 mol FeCl3·6H2O, 0.0025eCl2·4H2O and varied dextran were dissolved in 100 ml water.nder vigorous mechanical stirring (1200 rpm), the solution was

dded dropwise into a 100 ml ammonia solution which has beeniluted from 25% to 5% (wt). The process of dropping was sus-ained about 15 min, and another 15 min was kept with stirringo complete the reaction. All processes were kept in a nitro-en environment at room temperature. After the reaction, excess

mmonia and dextran macromolecules were rinsed by dialysissing the membrane bag with a 60000 cut-off molecular weightor about 48 h. The aqueous solution of dextran-Fe3O4 is verytable and there is no sediments appeared after weeks, which

2466

st references and proposed by us. A: Dextran-Fe3O4 clusters with a core-shellclusters proposed by us.

ndicate that the Fe3O4 nanoparticles have been completely sta-ilized by dextran. The resultant dextran-Fe3O4 clusters wereoncentrated by centrifugation (11000 rpm for 20 min) and thenried in a freezing drier at about −45 ◦C. Several kinds of sam-les were synthesized using different kinds of dextran, whichere listed in Table 1.

.3. Characterization

Size of the clusters dispersed in water was determined by aalvern HPPS particle sizer. TEM samples were prepared by

utting a drop of the as-prepared suspension on a carbon coatedopper grid and then dried in a desiccator. TEM observationas performed at 200 KV on a JEOL JEM-2010 transmission

lectron microscope. EDS was taken on an energy diffractionpectrometer (Oxford Instruments, UK) subsidiary to TEM. Themount of macromolecule adsorbed on the magnetite nanopar-icles was determined by a thermogravimetric analyzer (TGA)sing a TGA2050 (TA Instruments, USA) with a 20 ◦C/min

0E 2:1 200A 1:2.5 400A 1:2.5 60–900B 1:5 60–90

72 K. Tao et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 290 (2006) 70–76

20A a

Tp

3

3

ofwsowt

Auttnip

tid

Fig. 1. Typical TEM micrograph of dextran-Fe3O4 clusters: (a) sample

he magnetization study was performed using a vibrating sam-le magnetometer at room temperature.

. Results and discussion

.1. Morphology and size of dextran-Fe3O4 hybrid clusters

In TEM micrograph (Fig. 1), nanoparticles with a diameterf 2–5 nm can be seen, and these nanoparticles aggregate andorm clusters with a diameter of 20–300 nm. Similar clustersith various sizes were observed in almost all images of other

pecimens. EDS result of the black area indicated that what webserved is the hybrid clusters composed iron oxide and dextranithout other impurities. By using a method of laser scattering,

he size and size distribution of clusters can be got as Fig. 2.

mFtt

Fig. 2. Size distribution of clusters prepared by (a) dextrans with a molecular w

nd (b) sample 60A, inset in (b) is the EDS of the clusters in this image.

s the sizes mainly distributed in the range of 10–1000 nm,ndoubtedly the size distribution should be corresponding tohe agglomerated clusters but not the individual Fe3O4 nanopar-icles. That also means the clusters observed under TEM areot due to the aggregation of Fe3O4 nanoparticles during dry-ng process of TEM samples, but formed during the synthesisrocess of Fe3O4.

As can be seen in Fig. 2a, the polydispersity index of clus-ers, i.e., the number of both bigger clusters and smaller clusters,ncreased with more dextran were added in the preparation ofextran-Fe3O4 clusters. There are two opposite effect of adding

ore dextran in the preparation on the size of resultant dextran-e3O4 clusters. On one hand, macromolecule chains can prevent

he aggregation between clusters or Fe3O4 nanoparticles; onhe other hand, more macromolecular chains would cause the

eight of 20k, and (b) dextrans that 2.5 times in weight than iron cation.

hysicochem. Eng. Aspects 290 (2006) 70–76 73

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R

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K. Tao et al. / Colloids and Surfaces A: P

igher probability of tangling each other, and Fe3O4 nanoparti-les absorbed on the tangled macromolecular chains and mixedith them to form clusters, so that result in further growth of the

lusters. While in Fig. 2b, if the same dosage of dextran with var-ed molecular weight were used, almost no smaller clusters formut a small peak in the bigger size range can be observed, whichan also be easily interpreted by the absorption of particles onhe more tangled macromolecule chains.

How do the nanoparticles absorb on the macromoleculehains? As is well known, there should be two steps to formacromolecule-Fe3O4 hybrid clusters in coprecipitation: first

f all, nucleation and growth of Fe3O4 crystals, subsequently,urther aggregation of hydrophobic Fe3O4 crystals and sta-ilization of them by hydrophilic macromolecules. The firsttep is the key step decided the formation mechanism andhe structure of dextran-Fe3O4 hybrid clusters. If the Fe3O4mbryos prefer to nucleate in the macromolecular chains, itould be possible that several magnetite embryos coated onne macromolecular chain or one magnetite embryo coatedn the cross of several chains to immobilize them; so tangledacromolecular chains would connect nanoparticles each other

o form hybrid clusters. To explore the nucleation mechanismlteriorly, the trend of nucleation of Fe3O4 was calculated usingclassical theory of nucleation in next section.

.2. Classical theory of nucleation

In classic thermodynamic nucleation theory [17], the homo-eneous nucleus is conceived as an aggregate of critical sizehich is in unstable equilibrium with its parent phase. It is

ssumed that macroscopic properties may be assigned to such aucleus. The radius of the critical embryo,R∗

Hom and the activa-ion energy �G∗

Hom, are given by:

∗Hom = − 2σSL

�GV

nd

G∗Hom = 16πσ3

SL

3(�GV)2 ,

here �GV = (1/v)kT ln(a/aS), σSL is the solid/solution inter-acial energy, v the molecular volume, k the Boltzmann constant,and as are the activities of the solute in supersaturated solu-

ion and in equilibrium, respectively. The rate of homogeneousucleation, which is regarded as the rate of addition of the post-ritical ion to the critical nucleus, is given by:

N =(

dN

dt

)1

V= A exp

[−(�G∗Hom)

kT

]

hile in a macromolecule-contained system, flexible and ran-om coiled macromolecular chains supply the matrix for het-rogeneous nucleating of particles. The model like Fig. 3 gives

visualized schematic plan for the heterogeneous nucleation.s the same principle of homogeneous nucleation, the changef free energy of the system is consist of the increase of freenergy caused by volume change and the decrease caused by

nnpo

Fig. 3. The model of nanoparticles nucleating on a cambered surface.

he increase of interface. A complicated equation can be get as

G = VS�GV + �GS

= 4

3πR3�GVf2(α, θ) + 4πR2σSLf1(α, θ)

here

1(α, θ) = 1

2

[1 − cos(α + θ) − sin2(α + θ)

sin2α(1 − cos α)cos θ

]

nd

2(α, θ) = 1

4

[2 − 3cos(α + θ) + cos3(α + θ)

− sin3(α + θ)

sin3α(2 − 3cos α + cos3 α)

]

rom that, we can get the radius of critical embryo, R∗Het, given

y:

∗Het = − 2σSL

�GV

f1(α, θ)

f2(α, θ)= f1(α, θ)

f2(α, θ)R∗

Hom

he activation energy, �G∗Het, given by

G∗Het = 16πσ3

SL

3�G2V

f 31 (α, θ)

f 22 (α, θ)

= f 31 (α, θ)

f 22 (α, θ)

�G∗Hom

nd the rate of heterogeneous nucleation is RN =dN/dt)(1/V ) = A exp[−(�G∗

Het)/kT ].Functional images of the coefficients of R* and �G*

f1(α, θ)/f2(α, θ) andf 31 (α, θ)/f 2

2 (α, θ)] can be got by MAT-AB as Fig. 4. As α + θ cannot be greater than π, the trianglebove diagonal line is useless for us. Obviously, when α + θ = π,he value is on the diagonal and equal to 1. On the conditionf α + θ < π, the coefficients would increase with increase of θ

nd decrease of α. It should be pointed out that all values in themage were less than or equal to 1. That means heterogeneous

ucleation is more preferable than or equal to homogeneousucleation in energy. And, nucleation would more favorable hap-en on the big curvature surface than on the small one (decreasef α).

74 K. Tao et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 290 (2006) 70–76

cient

ntttrTsomiTcsm

wlioacnsitoldclwfabactt

i[

3

clSe2pwicBecause the remainder of the hybrid clusters as the temperaturehigher than 600 ◦C were composed with most Fe3O4 and lit-tle carbide from dextran, and the weight of the carbide fromdextran can be known from the weight loss curves of pure dex-

Fig. 4. Functional image of the coeffi

As the substrate for the heterogeneous nucleation of mag-etite, no matter what shape of macromolecule chains are inhe solution, nucleation would more easily happen. That iso say, the Fe3O4 embryos would prefer to grow from dex-ran chains in the coprecipitation process, and result in recip-ocal connection of Fe3O4 nanoparticles and dextran chains.hus, the Fe3O4/dextran hybrid clusters would form and theirizes could be affected by the content and molecular weightf dextran. Wetting angle (θ), obviously has relation to latticeatching between macromolecule and magnetite, is another

mportant parameter that can affect the trend of nucleation.he shape and size of nanoparticles can be controlled byhoosing the macromolecules with different boundary ten-ion to magnetite and modifying α by self-organization ofacromolecules.In most references, dextran stabilized Fe3O4 nanoparticles

ere suggested having a Fe3O4 core which surrounded by oneayer of hydrophilic dextran “shell” (as shown in Scheme 1A),t means dextran chains were attracted around Fe3O4 coresnly by non-covalent bonds, this structure can be realized onlyt the condition of the homogeneous nucleus is preferred inoprecipitation. However, the calculation based on a classicalucleation theory indicated that the heterogeneous nucleationhould be preferred instead of homogeneous nucleation. Accord-ng to the analysis of experiment results and classical nucleationheory, a novel mechanism of the formation and the structuref Fe3O4-dextran hybrid clusters can be summarized as fol-ows (Scheme 1B): When solution concluding Fe2+, Fe3+ andextran dropped into ammonia solution, most of nucleation pro-esses would happen on macromolecular chains, and nucleusesocated at curved site and crossing point of two or more chainsere preferred. Thus, most Fe3O4 nanoparticles would grow

rom dextran chains and lock the tangle of several chains. Withgrowth process progressed, these Fe3O4 nanoparticles woulde connected together by macromolecular chains and clusters

re formed. It should also be pointed out that macromolecularhains can be attracted on part surface of clusters, also preventhese clusters from more serious aggregation [7]. So the struc-ure of a Fe3O4-dextran hybrid cluster would be schematically

F2o

of (A) R* and (B) �G* vs. θ and α.

llustrated as Scheme 1B, which has been hinted in a reference18] without explicitly putting forward.

.3. Structure and magnetic property of clusters

Fig. 5 shows weight loss curves of dextran-Fe3O4 hybridlusters measured by thermogravimetric analyzer. Two weightoss stages were observed in thermograms of hybrid clusters.urely, the first stage (below 130 ◦C) can be ascribed to thevaporation of water, while the other one beginning at about40 ◦C is due to the decomposition of dextran. Thermograms ofure dextran with molecular weight of 20 k, 40 k and 60–90 kere also measured and shown in the inset of Fig. 5, which

ndicate that the differences between thermograms of samplesannot attribute to the difference of molecular weight of dextran.

ig. 5. Weight loss curves of specimens at a temperature increasing rate of0 ◦C/min in N2 atmosphere, inset is the weight loss curve at the same treatmentf pure dextran with molecular weight of 20 k, 40 k and 60–90 k, respectively.

K. Tao et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 290 (2006) 70–76 75

tw2TtmtnTdpfdohstac

tmbicmno

TCm

L

((((((

F

tb(

isddcndm

D

wou6fuTa

Fig. 6. XRD spectra of the samples prepared at different WCD.

ran shown in the insert of Fig. 5, it can be calculated that theeight ratio between magnetite and dextran in the specimens of0A, 40A and 60A is about 1:1.5, 1:2, and 1:2.15, respectively.hat means there are more dextran molecules participated in

he formation of dextran-Fe3O4 clusters with the increase of theolecular weight of dextran. Obviously, it can be attributed to

he dextran with higher molecular weight has more opportu-ities to be caught by Fe3O4 nanoparticles. By comparing theGA curves of three samples which were prepared at the sameosage (20A, 40A and 60A), it is obvious that the cluster pre-ared using the dextran with higher molecular weight have aaster decomposition velocity, which can be attributed to mostextran chains were tangled in the periphery but not the insidef the Fe3O4 nanoparticles in 60A. Additionally, sample 60Bas a lower decomposition rate, suggesting that there are moreegments of dextran chains existed inside Fe3O4 nanoparticleshan other samples. In a summary, the decomposition rate hasdirect relationship with the proportion of the macromolecularhains which exist inside the Fe3O4 nanoparticles.

The crystallite phase of dextran-Fe3O4 clusters were charac-erized by XRD. As shown in Fig. 6, the diffraction peaks of

agnetite nanoparticles in 20A and 40A were mostly depressedecause of the higher dextran content in these samples, whereasn the XRD spectrum of another sample with lower dextran

ontent (20E), the position and relative intensity of main peaksatch well with those from the JCPDS card (19-0629) for mag-

etite, indicating that magnetite rather than other kinds of ironxide was produced in our experiment (Table 2). We also found

able 2omparison of d-spacing values of Fe3O4 in sample 20E with standard JCPDSagnetite data

attice plane Standard d-spacingvalues of Fe3O4

d-spacing values ofsynthesized iron oxide

2 2 0) 2.967 2.9543 1 1) 2.532 2.5304 0 0) 2.099 2.0834 2 2) 1.714 1.7075 1 1) 1.615 1.6054 4 0) 1.484 1.480

c

tcmob

4

bmoim

ig. 7. Magnetization curves for the samples 20A, 20C, 40A and 60A at 298 K.

hat the nanoparticles would aggregate too seriously to keep sta-le if dextrans with a WCD = 2:1 were used in fabrication processsample 20E).

Magnetization curves measured at 298 K, which are shownn Fig. 7, show almost immeasurable coercivity and remanence,uggesting that these magnetite nanoparticles are of a singleomain. The saturation magnetizations of all samples have airect relationship with the z-average size of clusters; the biggerluster has a higher saturation magnetization. And, in case ofo hysteresis, the initial susceptibility, χi = (dM/dH)H→0, wasetermined by the size of nanoparitcles. An upper limit for theagnetic size, Dv, can be estimated using the formula [19]:

v =(

18kBT

πMs

√χi

3εMsH0

)1/3

here 1/H0 is the point where the high-field linear extrapolationf M versus 1/H crossed the abscissa, and ε is the particle vol-me fraction. The diameters of samples 20A, 20C, 40A and0A can be obtained as 6.2 nm, 6.5 nm, 5.2 nm and 5.5 nmrom magnetization measurements, respectively. For these val-es are closed to that of single nanoparticles estimated fromEM image, it maybe concluded that the magnetization curvesre corresponding to single nanoparticles rather than hybridlusters.

The saturation magnetizations of the particles are lower thanypical value for pure or surface modified Fe3O4 nanoparti-les, which usually in the range of 50–70 emu/g. The loweragnetization should be mainly attributed to the high content

f dextrans in hybrid clusters which form nonmagnetic layersetween Fe3O4 magnetic nanoparticles [20].

. Conclusions

We fabricated dextrans stabilized magnetite nanoparticlesy the coprecipitation method, and found that the content and

olecular weight of dextrans almost did not affect the size

f nanoparticles but affected that of clusters, which can benterpret by the structure model proposed in Scheme 1B. The

acromolecular chains can play the role as a substrate for the

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6 K. Tao et al. / Colloids and Surfaces A

ucleation of magnetite, thus to make the nanoparticles grown a dextran chain just like pearls on a necklace. Further-ore, these “necklaces” can aggregate as clusters. The clas-

ical nucleation theory also shows that the shape and size ofanoparticle could be affected by the shape of macromolec-lar chains and the interface tension between macromoleculend magnetite. And, we also found that the magnetization curvef these particles expressed immeasurable coercivity and rema-ence, suggesting that they are of single domain. Their satu-ation magnetizations closely correlate with the sizes of clus-ers.

cknowledgments

This work was financially supported by Science and Tech-ology Committee of Shanghai (Project No. 05ZR14084 androject No. 04dz14002) and Young Scholar’s foundation ofhanghai Jiao Tong University. We thank Instrumental Anal-sis Centre of SJTU for assistance with the instrumenta-ion.

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