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DMSA转化油相 Fe3O4

Available online at https://www.sodocs.net/doc/6d8012887.html, Colloids and Surfaces A:Physicochem.Eng.Aspects

316 (2008) 210–216

Preparation and characterization of water-soluble monodisperse magnetic iron oxide nanoparticles via surface double-exchange with DMSA

Z.P.Chen a,b,c,Y.Zhang a,b,S.Zhang a,b,J.G.Xia a,b,J.W.Liu a,b,c,K.Xu a,b,c,N.Gu a,b,?

a State Key Laboratory of Bioelectronics,Southeast University,Nanjing210096,PR China

b Jiangsu Laboratory for Biomaterials and Devices,Nanjing210096,PR China

c School of Chemistry an

d Chemical Engineering,Southeast University,Nanjing210096,PR China

Received20April2007;received in revised form17August2007;accepted1September2007

Available online 12 September 2007

Abstract

A simple,but ef?cient method for preparation of water-soluble iron oxide nanoparticles has been developed.Monodisperse Fe3O4nanoparticles were synthesized by thermal decomposition of iron-oleate.Surface double-exchange of oleic acid capped monodisperse Fe3O4nanoparticles with a familiar2,3-dimercaptosuccinnic acid(HOOC–CH(SH)–CH(SH)–COOH,DMSA)was?rst performed in chloroform in the presence of triethylamine,and then this process was repeated in ethanol under the same conditions.The resulting Fe3O4nanoparticles could be transferred into water to form stable magnetic?uid without post-treatment processes such as?ltration and re-concentration.TEM images show that water-soluble Fe3O4nanoparticles remain monodisperse and even form a monolayer of ordered assembly,and the results of TGA,VSM show that Fe3O4 nanoparticles via surface double-exchange possess more DMSA molecules through intermolecular disul?de cross-linking between DMSA,as con?rmed by Raman spectra.Zeta potential measurements show that nanoparticles after surface double-exchange are negatively charged in the range of pH=1–14,and stability assays exhibit their excellent stability in water and other physiological environments.

Keywords:Monodisperse;Iron oxide nanoparticle;DMSA;Surface double-exchange;Water-soluble

1.Introduction

Magnetic nanoparticles have been widely studied because of their many biological applications such as magnetic sepa-ration[1,2],DNA detection[3],magnetic resonance imaging [4,5],target-drug delivery[6],and magnetic hyperthermia[7,8]. Among magnetic nanoparticles,iron oxide nanoparticles are of particular interests for applications because of their unique mag-netic properties and biocompatibility.For future highly sensitive magnetic nanodevices and biological applications,iron oxide nanoparticles with controlled-shape,-size,and a narrow size dis-tribution are urgent.Very recently,several groups have reported that such high-quality iron oxide nanoparticles could be syn-thesized by thermal decomposition of different types of iron precursors such as iron acetylacetonate[9],iron pentacarbonyl ?Corresponding author at:State Key Laboratory of Bioelectronics,Southeast University,Nanjing210096,PR China.Tel.:+862583794960;

fax:+862583792576.

E-mail address:guning@https://www.sodocs.net/doc/6d8012887.html,(N.Gu).[10],and iron-oleate[11,12].However,the direct products of the above-mentioned approaches are organic-soluble,which to some extent limits their applications in biological?elds.

To take advantage of their high-quality properties in biological applications,it is necessary to transfer iron oxide nanoparticles from organic to aqueous solution.Some groups have reported surface modi?cation techniques including surface exchange with cyclodextrin[13],copolypeptides[14], anionic octa(tetramethylammonium)-polyhedral oligomeric silsesquioxane(TMA-POSS)[15],and intercalation of surfac-tants[16].Especially,some reports have given prominences to surface exchange with DMSA by which iron oxide nanoparticles modi?ed are fairly stable in water over wide ranges of pH and salt concentrations[4,5,17–20],which makes them preferable in biological applications.From the point of surface chemistry, the success of any surface exchange process relies on a careful balance of the intermolecular forces driving the interaction between the molecules to be exchanged and the outermost layer of the substrate surface.Bruce et al.reported an inexpensive method for the introduction of more amino groups onto the

Z.P.Chen et al./Colloids and Surfaces A:Physicochem.Eng.Aspects 316 (2008) 210–216211

surface of silica-coated iron oxide nanoparticles under various

reaction conditions such as solvent systems and temperatures

[21].Here,we developed surface double-exchange of oleic acid

capped monodisperse Fe3O4nanoparticles with DMSA in the

presence of triethylamine.The resulting Fe3O4nanoparticles

could be transferred into water to form stable magnetic?uid

without post-treatment processes and kept stable for several

months,even at high concentration.

2.Experimental

2.1.Materials

1-octadecene was purchased from Alfa Aesar.4-

Morpholineethanesulfonic acid(MES)was purchased from

Pierce and RPMI-1640was purchased from Gibco.Note that

RPMI-1640used in our experiments contains10%(v/v)fetal

calf serum.The other chemicals were analytical reagents and

purchased from Shanghai Chemical Reagent Corporation,

China.All chemicals were used as received.Distilled water

was used for all the experiments.

2.2.Synthesis of monodisperse Fe3O4nanoparticles

Known method was followed to synthesize monodisperse

Fe3O4nanoparticles[11].Monodisperse Fe3O4nanoparticles

were synthesized in two steps:?rst,to prepare an iron-oleate

precursor and second,to decompose the precursor.In a typi-

cal experiment,2.7g of FeCl3·6H2O was dissolved in50mL of methanol followed by addition of8.5mL oleic acid.And

then,a solution with1.2g of NaOH in100mL of methanol was

dropped into above solution under magnetic stirring conditions.

The observed brown precipitate was washed with methanol4–5

times and dried under vacuum overnight to remove all solvents.

The obtained waxy iron-oleate was dissolved in1-octadecanol

at70?C and reserved as a stable stock solution at room temper-

ature.

One millilitre of the above stock solution(0.39mol/mL)was

mixed with4mL1-octadecanol and0.5mL oleic acid.The reac-

tion mixture was heated to320?C at a constant heating rate

of3.3?C/min under a nitrogen atmosphere,and then kept at

that temperature for30min.The resulting solution was cooled

and precipitated by addition of excess ethanol and centrifuga-

tion.And then,the precipitate containing Fe3O4nanoparticles

was washed4–5times with ethanol.This sample was labeled as

MNP-1.

2.3.Preparation of water-soluble Fe3O4via surface

double-exchange

One hundred milligrams of MNP-1was dissolved in10mL

chloroform followed by addition of50?L triethylamine.Fifty

milligrams of DMSA was dispersed in10mL dimethyl sulfox-

ide(DMSO).And the solution was added into the above solution

containing MNP-1.The resulting solution was vortexed at60?C

for12h.The solution became turbid,and the black precipitate

was observed.The?nal sample labeled as MNP-2was obtained by centrifugation,followed by washing with ethanol carefully, and dissolved in10mL water for characterization and com-parison.This process was repeated,and obtained MNP-2was dissolved in100mL ethanol for next reaction.

We found that MNP-2was more easily dissolved in ethanol than water,so surface double-exchange was repeated in ethanol to introduce more DMSA molecules onto the surface of Fe3O4 nanoparticles.Especially,50?L triethylamine was added into above ethanol solution containing MNP-2,followed by addition of a solution with50mg DMSA in10mL DMSO.The solution was vortexed at60?C for12h.The?nal sample labeled as MNP-3was centrifuged and washed with ethanol4–5times carefully. MNP-3was collected using a permanent magnet and transferred into10mL water.

2.4.Characterization

The size and morphology of the particles were determined by a JEM-2000EX TEM operating at120.0kV.Samples were dropped,either from chloroform or water,onto a carbon-coated copper grid and dried under room temperature.IR spectra were recorded on a Nicolet Nexus870FT-IR spectrometer and pow-der samples were dried at100?C under vacuum for24h prior to fabrication of the KBr pellet.Spectra were recorded with a resolution of2cm?1.Raman spectra were collected on a JY HR800spectrometer with a resolution of1cm?1.Thermo-gravimetric analysis(TGA)was performed for powder samples (～5mg)with a heating rate of20?C/min using a Perkin-Elmer TGA7Thermogravimetric Analyzer in synthetic N2atmosphere up to700?C.Magnetic measurements were carried out with a Lakeshore7470vibrating sample magnetometer(VSM).

Photon correlation spectroscopy(PCS)was used to determine hydrodynamic size distribution using a Beckman Coulter N4 Plus Submicron Particle Analyzer,and surface charge measure-ments were performed with a Beckman Coulter Delsa440SX Zeta Potential Analyzer.Furthermore,to investigate stability of MNPs dispersed in different media,1mL MNP-2solution was added to four50mL beakers containing50mL water, RPMI-1640,PBS and MES buffer solution,respectively.The suspension was settled at room temperature and the upper solu-tion was taken to record UV–visible absorbance spectra every day for5days[15],using a U-4100spectrophotometer.Stability assays for MNP-3were performed as above-mentioned process.

3.Results and discussion

3.1.TEM

Monodisperse Fe3O4nanoparticles(MNP-1)were synthe-sized by thermal decomposition of iron-oleate in the presence of oleic acid.TEM image(Fig.1a)shows that MNP-1is monodis-perse with about10nm average diameter and well-dispersed in chloroform.According to the ED pattern(Fig.1b),the d-spacing can be calculated in the following equation:

Lλ=dR

where L is the distance between the test sample and the?lm (L=137cm),λthe wavelength of electron beam(λ=0.0251A?)

212Z.P .Chen et al./Colloids and Surfaces A:Physicochem.Eng.

Aspects 316 (2008) 210–216

Fig.1.(a)TEM image of MNP-1dispersed in chloroform;(b)ED image of MNP-1;(c)TEM image of MNP-3dispersed in water;(d)enlarged image of region marked with the arrow in (c).

and R is the radius of the diffraction ring.The calculation results are shown in Table 1,which are well accorded with theory values of the inverse cubic spinel structure of Fe 3O 4.Water-soluble Fe 3O 4nanoparticles (MNP-3)were prepared in chloroform followed by repeated performance in ethanol via surface double-exchange with DMSA in the presence of tri-ethylamine.TEM images (Fig.1c and d)show that MNP-3is well dispersed in water (the TEM image of MNP-2is not provided because there is no obvious differences between MNP-2and MNP-3).In addition,these images indicate that no degradation takes place upon transfer from organic to aqueous solution.

3.2.IR and Raman

IR spectra of MNP-1,MNP-2,MNP-3and pure DMSA are shown in Fig.2.IR spectra for all samples exhibit one interest-ing region located between 1800and 1500cm ?1.In spectrum a,the sharp peak at 1715cm ?1assigned to carbonyl indicates that there is free oleic acid [22]and the two peaks at 1569and 1519cm ?1due to the symmetric and asymmetric carboxylate (COO ?)stretch,respectively,indicate that oleic acid is bound to the surface of Fe 3O 4nanoparticles through covalent bond between carboxylate (COO ?)and Fe atom [23–25].The appear-ance of a broad peak at 1580cm ?1in spectrum b and two broad

Table 1

ED experimental data of MNP-1in comparison with theory values

234567R (cm)

0.70 1.16 1.36 1.64 2.01 2.12 2.32ED results,d (?A) 4.89 2.95 2.52 2.09 1.70 1.62 1.48Theory values,d (?A)

4.85 2.97 2.53 2.10 1.71 1.62 1.48Crystalline lane (h l k )

(111)

(220)

(311)

(400)

(422)

(511)

(440)

Z.P.Chen et al./Colloids and Surfaces A:Physicochem.Eng.Aspects 316 (2008) 210–216

213

Fig.2.IR spectra of(a)MNP-1,(b)MNP-2,(c)MNP-3and(d)DMSA. peaks at1670and1580cm?1in spectrum c derived from the symmetric and asymmetric stretch of carboxylate(COO?)of DMSA indicates that DMSA is bound to the surface of Fe3O4 nanoparticles.In spectrum d,the weak peak at2562cm?1is attributed to thiol group and the sharp peak at1700cm?1is assigned to the carbonyl stretch of DMSA as a diacid.Therefore, the appearance of the low frequency of the peak at1711cm?1 both in spectra b and c,compared to the frequency for free oleic acid(1715cm?1),is attributed to free carbonyl stretch of DMSA on the surface of Fe3O4nanoparticles.Additionally,the presence of the sharp methylene peaks at2922and2854cm?1,in spectra a–c,indicates that some of initial oleic acid remains on the sur-face of Fe3O4nanoparticles after modi?cation.The reason of the lack of evidence of thiol group and disul?de group,in spectra b and c,is that most of thiol groups have been oxidated into disul-?de groups which are lower absorption in IR analysis.So Raman spectra are used to con?rm disul?de groups,as shown in Fig.3. No peak is observed for MNP-1between300and800cm?1,

whereas a sharp peak for MNP-3appears at about503cm?1

Fig.3.Raman spectra of MNP-1and

MNP-3.

Fig.4.TGA curves of MNP-1,MNP-2and MNP-3.

due to strong absorption of disul?de groups.This result sug-

gests that intermolecular disul?de cross-linking between DMSA

molecules can introduce more DMSA molecules onto the sur-

face of nanoparticles.

3.3.TGA

TGA has been performed to con?rm the coating formation

and estimate the binding ef?ciency on the surface of Fe3O4

nanoparticles.Fig.4shows the weight loss for MNP-1,MNP-2

and MNP-3.A slight weight loss is observed up to250?C in

all curves,probably due to adsorbed water,while a signi?cant

weight loss takes place between250and500?C.The weight loss

for MNP-1,attributed to decomposition of oleic acid,is about

25%,corresponding to a monolayer of oleic acid on the surface

[26].The weight loss for MNP-2and MNP-3is increased to

34%and65%,respectively,mainly due to the decomposition of

DMSA.Interestingly,the molecular weights of oleic acid and

DMSA are282and182,respectively.Assuming one DMSA

molecule exchanged with one oleic acid molecule,the weight

loss for both of MNP-2and MNP-3should be13.6%in contrast

with MNP-1,while if one DMSA molecule exchanged with two

oleic acid molecules,the weight loss for them should be7.8%.

Therefore,the increased weight loss for MNP-2and MNP-3

suggests that a multilayer of DMSA exists on their surfaces.

Especially,the more signi?cant weight loss for MNP-3than

MNP-2(69%:39%)shows that more DMSA molecules exist on

the surface of MNP-3.

3.4.Magnetic measurements

Magnetic measurements indicate superparamagnetic behav-

ior at room temperature for all samples,with no hysteresis and

perfect Langevin behavior(Fig.5).The saturation magnetization

value(M s)for MNP-1is50.2emu/g,while the M s for MNP-2

and MNP-3are decreased to33.4and16.6emu/g,respectively.

There are several approaches that can explain the reduction of

the M s for coated magnetic nanoparticles[27–29].In this case,

214Z.P.Chen et al./Colloids and Surfaces A:Physicochem.Eng.Aspects 316 (2008) 210–216

Table2

The M S for Fe3O4cores based on TGA and VSM results

Sample Percentage of Fe3O4core(%determined by TGA)Total M S(emu/g;determined by VSM)The M S of Fe3O4core(emu/g) MNP-17250.269.72

MNP-26133.454.75

MNP-33116.6

53.55

Fig.5.Hysteresis loops at room temperature for MNP-1,MNP-2and MNP-3.

the presence of nonmagnetic DMSA molecules on the surface of MNP-2and MNP-3leads to decrease of the M s,and more decrease of the M s for MNP-3than MNP-2indicates that there are more nonmagnetic DMSA molecules on the surface of MNP-3,which is consistent with TGA results.Furthermore,since the weight percentage for Fe3O4core is about72%,61%,31%, determined by TGA,the M s for Fe3O4cores of MNP-1,MNP-2and MNP-3are69.72,54.75,and53.55emu/g,respectively (Table2).

3.5.Stability assays

Fig.6shows hydrodynamic size distribution of MNP-2and MNP-3.The average hydrodynamic sizes of MNP-2and MNP-3are about250and320nm,respectively,indicating that both of MNP-2and MNP-3exist as aggregates in water.However, smaller hydrodynamic size of MNP-3than MNP-2suggests that MNPs-3be of better stability.Zeta potential results(Fig.7)show that MNP-3is always negatively charged in the range of pH 1–14,whereas MNP-2has an isoelectric point(IEP)at pH1.62, indicating that total charge of DMSA molecules on the surface keeps MNP-3sterically and electrically stable in water.

Many biological applications require magnetic nanoparticles to exhibit stability in physiological environments,so we inves-tigate stability of MNP-2and MNP-3in water,RPMI-1640(a complex medium for cell culture)and two kinds of buffer solu-tions(MES and PBS)based on UV–visible absorbance(Fig.8). After settling for5days,for MNP-2dispersed in water,MES, PBS,UV–visible absorbance changes from0.294,0.303and 0.31to0.089,0and0,respectively(Fig.8a).While for MNP-3, it changes from0.289,0.303and0.306to0.168,0.101and

0.12,Fig.6.Hydrodynamic size distribution of MNP-2and MNP-3dispersed in water.

respectively(Fig.8b).These results indicate that MNP-3is more stable than MNP-2in water and physiological environments. Interestingly,UV–visible absorbance of MNP-2dispersed in RPMI-1640changes to0after5days,indicating that there are almost no Fe3O4nanoparticles in the upper solution.How-ever,UV–visible absorbance of MNP-3dispersed in RPMI-1640 changes from0.328to0.251,indicating that it is the most stable for all the samples.

3.6.Structure and water-solubility test

In our surface double-exchange reactions,DMSA is used to exchange with long-chain oleic acid on the surface of Fe3O

4 Fig.7.Zeta potentials of MNP-2and MNP-3.

Z.P.Chen et al./Colloids and Surfaces A:Physicochem.Eng.Aspects 316 (2008) 210–216

215

Fig.8.Stability assays of MNP-2(a)and MNP-3and(b)dispersed in water, RPMI-1640(pH7.0),PBS(pH7.4)and MES buffer solution(pH4.9),respec-tively.

nanoparticles.Furthermore,it is noticeable that alkalescent tri-ethylamine plays an important role as catalyst.It can deprive of hydrogen ions of carboxyl of DMSA to form carboxylate which is preferable to exchange with long-chain oleic acid.The surface double-exchange reaction without triethylamine was carried out for comparison,and we found that the resulting Fe3O4nanoparticles were not stable in water at high concentra-tion(data not provided).DMSA is exchanged onto the surface of nanoparticles by at least one carboxyl.DMSA?rst forms a stable coating through its carboxylic chelating bonding and further stability is obtained through intermolecular disul?de cross-linking between DMSA molecules.The remaining car-boxylates ensure surface charges and can be used for conjugating with biological molecules and further applications.Fig.9a is schematic illustration for the structure of Fe3O4nanoparticles modi?ed by DMSA.We consider that the difference between MNP-2and MNP-3is the amount of DMSA on the surface of Fe3O4nanoparticles,as con?rmed by TGA,VSM and water-solubility test(Fig.9b).Although no precipitate is observed when both of MNP-2and MNP-3are dispersed in water at the high concentration of10mg/mL,MNP-2is precipitated thoroughly and MNP-3remains stable after10days,

which Fig.9.(a)Schematic illustrations for the structure of MNP-2and MNP-3and (b)water-solubility test of MNP-2and MNP-3.

indicates that the surface of MNP-3possesses more DMSA molecules.

4.Conclusions

Oleic acid capped monodisperse Fe3O4nanoparticles have been successfully transferred into aqueous solution via surface double-exchange with DMSA in the presence of triethylamine. The characterization results show that surface double-exchange is an ef?cient method that can introduce more DMSA molecules onto the surface of nanoparticles through intermolecular disul-?de cross-linking between DMSA.By this means,we obtain stable nanoparticles with negative charges in the range of pH=1–14.Moreover,the resulting products can be dispersed in water and other physiological solutions.Because DMSA is a nontoxic and biocompatible product used in many applications, high-quality magnetic nanoparticles modi?ed by DMSA by this means may be promising in biologically relevant applications. Acknowledgments

This work has been carried out under?nancial support of the National Natural Science Foundation of China(Nos.60571031, 60501009and90406023)and National Basic Research Pro-gram of China(Nos.2006CB933200and2006CB705600).The author would like to thank Mr.A.Q.Xu,from the Analy-sis and Testing Centre of Southeast University for technique assistances.

216Z.P.Chen et al./Colloids and Surfaces A:Physicochem.Eng.Aspects 316 (2008) 210–216

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DMSA转化油相 Fe3O4

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