RESEARCH IRON OXIDE NANOPARTICLES

SynthesisofIronOxideNanoparticleswithBiologicalCoatings
DavidDozier,SoubantikaPalchoudhury,*YupingBao,Ph.D. *FacultySponsor
DepartmentofChemicalandBiologicalEngineering,TheUniversityofAlabama,Tuscaloosa,AL35487,USA

For biological and biomedical applications, it is required to produce nanoparticles that are water soluble and biocompatible.Here,wereportthesynthesisofironoxidenanoparticlescoatedwithbiologicalmolecules(e.g., gluconic acid, lactobionic acid, or polyacrylic acid) via a coprecipitation method. These nanoparticles have narrow size distribution and are highly water soluble. Because of the biological coatings, they will have great potentialinnumerousbiomedicalapplicationssuchastissueengineering. Introduction continuedatthattemperaturefor20minutesbefore Magnetic nanoparticles have shown great theflaskwasremovedfromheatingandstirring.The potential in many biological and biomedical nanoparticles were then removed from solution by applicationssuchastargeteddrugdelivery,magnetic magnetic separation. During synthesis, the fluidhyperthermia,magneticresonanceimaging,and concentration and amount of NaOH was varied to tissue engineering [1, 3, 5, 6]. All these applications control the particle size. A schematic drawing of the require magnetic nanoparticles to be water soluble reactionsetupisshowninFigure1. andbiocompatible. For biological and biomedical applications, magnetic iron oxide nanoparticles are the primary choicebecauseoftheirbiocompatibilityandchemical stability.Manysynthesismethodshavebeenexplored for magnetic iron oxide nanoparticles. These include organic solvent heating method, polyol method, and coprecipitationmethod[2,4,7].Thecoprecipitation methodisthemosteffectivetechniqueforpreparing aqueous dispersions of iron oxide nanoparticles becausethesynthesisisconductedinwater.Forthis report, we studied several biological molecules as surface coatings to achieve biocompatibility such as gluconic acid (GA), lactobionic acid (LBA), and polyacrylicacid(PAA).Thesemoleculeswereusedto controltheparticlesize,topreventthenanoparticles fromaggregation,andtoachievebiocompatibility. Figure1.Schematicdrawingoftheexperimentalsetup. Experimental Surfacecoatings Synthesis After synthesis, the black precipitates were Ironoxidenanoparticlesweresynthesizedbya collected, washed with DI water, and then re modified coprecipitation method. Ferric chloride (FeCl3, 0.074g)andferrouschloride(FeCl2,0.190g) dispersed into 10 mL GA, LBA, or PAA solutions (100 ataratioof2to1weredissolvedin20mLdeionized mM) under sonication. The pH was adjusted to 8 in water, which was then stirred and heated to 60 C. order to simulate a biological environment and The solution was bubbled with Argon gas to prevent facilitate surfactant attachment to the iron oxide unwanted oxidation. Subsequently, 10 mL of 2.5 M nanoparticles. Three hours of sonication were NaOHsolutionwasinjectedat60Candthereaction required to obtain well dispersed nanoparticles. The
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nanoparticle solutions were then left at room temperature. Characterization Thesizeandmorphologyofnanoparticleswere studied by transmission electron microscopy (TEM); the crystal structure was verified using xray diffraction (XRD); the hydrodynamic size of the nanoparticles in solution was studied using dynamic lightscattering(DLS).Thesolutionswerealsochecked for precipitation. Solutions with a high level of precipitate indicated aggregation of nanoparticles. These aggregates are not suitable for biological applications. ResultsandDiscussion Figure 2 shows the representative TEM images of iron oxide nanoparticles coated with GA and LBA. Althoughthesizesofbothtypeswereroughly10nm, the GA coated nanoparticles were more dispersed than the LBA coated nanoparticles, which showed a certaindegreeofaggregation.

were fully oxidized either during or after the synthesis.

(311) (200)

Intensity (a.u.)

(400)

(440)

20

30

2 theta (degree)

40

50

60

70

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Figure3.XRDscanofironoxidenanoparticles.

For biological applications, nanoparticles are normally used in solution form. Therefore, it is important to study their hydrodynamic size in solution. DLS was used to measure the size of the synthesized nanoparticles. GA produced the smallest particles,showingapeakaround90nm.LBAandPAA bothhadpeaksaround140nmasshowninFigure4. The hydrodynamic sizes of the synthesized nanoparticles were significantly larger than those indicatedbytheirTEMimages.Thisispossiblydueto the hydrogen bond formation between the carboxyl groups on adjacent surfaces, which can cause cross linking between particles and result in a large hydrodynamicsize.ThesizefromDLSdidnotreveala large difference between the MNPs synthesized with 2.5MNaOHand5MNaOH.
15 PAA LBA GA

Figure 2. TEM images of iron oxide nanoparticles coated with(A)GAand(B)LBA.

The TEM image was not produced for the PAA coated iron oxide nanoparticles due to the large amount of the polymers present on the TEM grid, which interfered with the electron beam. However, the nanoparticle solution was well dispersed with no evident precipitate. Normally, precipitation is an indicationofaggregationofnanoparticles. The crystal structures of these nanoparticles were studied on GA coated nanoparticles. It was confirmed that these iron oxide nanoparticles are maghemite (Fe2O3), as shown in Figure 3, instead of the commonly formed magnetite nanoparticles (Fe3O4). This study suggests that the nanoparticles
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Intensity (%)
10

100

200 300 Diameter (nm)

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Figure4.DLSplotsofironoxidenanoparticlescoatedwith GA(cross),LBA(triangle),andPAA(circle).

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RESEARCH IRON OXIDE NANOPARTICLES

Conclusion In conclusion, water soluble iron oxide nanoparticles were synthesized using a co precipitation method. These nanoparticles were subsequentlycoatedwith GA,LBA,orPAA.BothGA and LBA coatings produced well dispersed nanoparticles.Theywereinfullyoxidizedoxideform asconfirmedbyXRD.Insolution,thesenanoparticles showed a much larger hydrodynamic size, possibly duetohydrogenbondformation.
References [1] BabesL,DenizotB,TanguyG,LeJeuneJJ&JalletP. (1999).Synthesisofironoxidenanoparticlesusedas MRIcontrastagents:Aparametricstudy.Journalof ColloidandInterfaceScience,212(2):474482. [2] GeJP,HuYX,BiasiniM,DongCL,GuoJH,Beyermann WP & Yin YD. (2007). Onestep synthesis of highly watersoluble magnetite colloidal nanocrystals. ChemistryaEuropeanJournal,13(25):71537161. [3] GuFX,KarnikR,WangAZ,AlexisF,LevyNissenbaum E, Hong S, Langer RS & Farokhzad OC. (2007). Targeted nanoparticles for cancer therapy. Nano Today,2(3):1421. [4] Hyeon T. Chemical synthesis of magnetic nanoparticles. (2002). Chemical Commun., 8:927 934. [5] Shimizu K, Ito A, Arinobe M, Murase Y, Iwata Y, Narita Y, Kagami H, Ueda M & Honda H. (2007). Effective cellseeding technqiue using magnetite nanoparticles and magnetic force onto decellularized blood vessels for vascular tissue engineering. J. of Bioscience and Bioenginer., 103(5):472478. [6] ThiesenB&JordanA.(2008).Clinicalapplicationsof magnetic nanoparticles for hyperthermia. InternationalJ.Hyperthermia,24(6):467474. [7] WenguangY.TonglaiZ,JianguoZ,JinyuG&Ruifeng W. (2007). The preparation methods of magnetite nanoparticles and their morphology. Progress in Chemistry,19(6):884892.

David Dozier is a junior from Thomasville, Alabama, majoring in chemical engineering with a minor in biology. He currently works in the laboratory of Dr. Yuping Bao in the Department of Chemical and BiologicalEngineering. David also has an interest in going to medical school after graduation. He is a Presidential Scholar and a member of the Golden Key HonorSociety.
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