Hasmonay, Preparation and properties of monodisperse magnetic fluids, Journal of Magnetism and Magnetic Materials 149 1995 1–5.. Wu, Preparation and characterization of magnetic polymer n
Trang 1j ou rn a l h o m e pag e :w w w e l s e v i e r c o m / l o c a t e / c o l s u r f a
Tai Thien Luonga, Thu Phuong Hab, Lam Dai Tranb,∗, Manh Hung Dob, Trang Thu Maib,
Nam Hong Phamb, Hoa Bich Thi Phanb, Giang Ha Thi Phamc, Nhung My Thi Hoangc,
Quy Thi Nguyenc, Phuc Xuan Nguyenb,∗
a Faculty of Chemistry, Hanoi National University of Education, Hanoi, Viet Nam
b Institute of Materials Science, Vietnam Academy of Science and Technology, Hanoi, Viet Nam
c Faculty of Biology, Hanoi University of Science, Vietnam National University, Viet Nam
a r t i c l e i n f o
Article history:
Received 14 December 2010
Received in revised form 14 February 2011
Accepted 22 February 2011
Available online 26 March 2011
Keywords:
Carboxylated Fe 3 O 4 ferrofluids
Poly(styrene-co-acrylic acid)
Magnetic heating effect
a b s t r a c t
© 2011 Elsevier B.V All rights reserved
Intherecentyears,magneticnanoparticles(NPs)haveattracted
a considerable attention of scientists working in the fields of
medicine and biotechnology Thanks to their unique magnetic
propertiesmagneticparticlescanbeutilizedexclusivelyinsome
special medical techniques,mostnotably, separation for
purifi-cationand immunoassay,drugdeliveryandtargeting,magnetic
resonance imaging (MRI), and hyperthermia [1–4] Among the
magneticmaterialsFe3O4NPsaremostfrequentlychosenbecause
ofthefollowingreasons:(i)Fe3O4isbiocompatible,(ii)Fe3O4NPs
canbesynthesizedatlargescale;(ii)themagnetizationofFe3O4
NPsissignificantlyhigh,thusallowingtheseparticlestobeeasily
controlledbyanexternalmagneticfield
Hyperthermiaisapromisingapproachtocancertherapy
How-ever,thetechnicalchallengewithhyperthermiaistoheatlocally
tumorregiontothedesiredtemperaturewithoutdamagingthe
surroundinghealthytissues It involvestheintroductionof
fer-romagneticorsuperparamagneticparticlesintothetumortissue
∗ Corresponding authors Tel.: +84 4 37564129; fax: +84 438360705.
E-mail addresses: lamtd@ims.vast.ac.vn (L.D Tran), phucnx@ims.vast.ac.vn
(P.X Nguyen).
andthenirradiationwithanACmagneticfield.Theheatingofthe cancerareacontainingmagneticNPstotheelevatedtemperatures (41–46◦C)inanexternalACmagneticfieldinducesapoptosisof tumorcells.TheparticlestransformtheenergyoftheACmagnetic fieldintoheatandthetransformationefficiencystronglydepends
onthefrequencyoftheexternalfieldaswellasthenatureofthe particlessuchasmagnetismandsurfacemodification[5–8] Theoretically,theproductionofheatbymagneticsubstancein
anexternalalternatingmagneticfieldmaybecausedbyseveral lossprocesses[9,10].First,hysteresismechanismofheat genera-tionoccursduringreversalofthemagnetizationandisrepresented
bytheareaofhysteresisloop,relatedtoanisotropyenergydensity
K,particlesizeandmicrostructure.Thesecondmechanismof mag-neticheatingisrelatedtothermalfluctuationwhentheparticle sizedecreasestobelowthesuperparamagneticcriticalvalue.The energyisdissipatedwhentheparticlemomentrelaxestoits equi-libriumorientation.Thisso-calledNéelrelaxationisdeterminedby theratioofKVtothethermalenergykT
N=0 exp
KV
kT
NeelrelaxationisrelatedtothelosspowerPasfollows: P(H,f)=21
kTH 2
fM2V fN
1+fN2
(2) 0927-7757/$ – see front matter © 2011 Elsevier B.V All rights reserved.
Trang 2as:
eff=N×B
N+B
(5) Experimentally,magneticheatingisdescribedbytemperature
increaseversusheatingtimecurve.Heatingcapacityis
character-izedbysocalledspecificlosspower(SLP),whichisproportional
totheinitialslopeoftheheatingcurve,accordingtothefollowing
equation:
SLP=Cms
mi
dT
whereCandms,are,respectively,theheatcapacityandmassofthe
ferrofluid;miisthemassofmagneticNPs.Accordingly,SLPofthe
magneticmaterialshouldbeashighaspossibleinordertoreduce
thedosebeingappliedtothepatienttoaminimumlevel
Fromanotherpointofview,exceptforhavingsuchproperties
ashighsaturationmagnetization,uniformparticlesizeand
super-paramagneticbehaviorofmagneticNPs,biomedicalapplications
requiremagneticNPstobecappedand/orsurfacefunctionalizedby
low-toxic,biocompatiblelayerswhichcouldprovideasteric
bar-riertopreventnanoparticleagglomerationandavoidopsonization
(theuptake bythereticuloendothelial system(RES), shortening
circulationtimeinthebloodandNP’sabilitytotargetthedrug
tospecificsitesandreducesideeffects).Secondly,thesecoatings
offerameanstotailorthesurfacepropertiesofNPssuchas
sur-facechargeandchemicalfunctionalitysothatbioactivesubstances
(enzyme,antibody,proteinandnucleicacid)couldbeboundto
theirsurfacewiththeaidofcouplingreagents(glutaraldehyde,
car-bodiimide,N-hydroxysuccinimide) Therefore, functional groups
(suchas–COOH,–NH2,–OHand –CHO) playanimportant role
inconjugatingpolymer-coatedmagneticNPswithbiomolecules
Inthiscontext,acrylicacid(AA),aninexpensivesubstancehaving
quitelowtoxicityandpossessingcarboxylatedgroupswas
prefer-entiallychosenasafunctional/protectiveshellinthecopolymeric
encapsulationwithstyrene(St)[5–7]
In this study, we do not take upon ourselves to introduce
novelmagnetic core/protective polymericshellsbut emphasize
oureffortsondesigningstablefluidswithlowtoxicityand
tun-ablemagneticheatingeffectforhyperthermictreatment.Namely,
Fe3O4/poly(St-co-AA)ferrofluidwaspreparedbydispersion
poly-merization, a special precipitation polymerization occurring
in a homogeneous system (ethanol/water medium) involving
monomers(St,AA),stabilizerand initiatorbeforereaction,with
Fe3O4magneticparticleasacoreandpoly(St-co-AA)asashell
Fe3O4corewasfirstobtainedbycoprecipitationandthen
encap-sulatedeitherbyinsituorexsitucopolymerizationwithStandAA
units.–COOHfunctionalizedshellplayeddualroleofstabilizingand
biomolecule-linkingroles.Toinvestigatewhetherthefluidscould
beusedadvantageouslyforbiomolecularbindingweused
Hepati-tisBsurfaceantibody(HBsAb)asbioconjugatingproteintakinginto
4 2 2 8 ammonia(NH3),hydrochloricacid(HCl),acetone((CH3)2CO)were
ofanalyticalgradeandusedasreceived.Phosphatebuffersaline (PBS), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), hepatitisBsurfaceantibody(HBsAb)werepurchasedfromSigma andusedasreceived
2.1.1 PreparationofmagneticFe3O4nanoparticles
Fe3O4 nanoparticles were synthesized by co-precipitation method of Fe3+ and Fe2+ under alkaline condition [11] Briefly, coprecipitation reaction is as follows: FeCl2+2FeCl3+ 8NaOH→Fe3O4+8NaCl+4H2O 4ml of 1M FeCl3, 2ml of 1M FeCl2and44mlof2MHClweretransferredintoathreeneckflask Thesolutionwasvigorouslystirredundernitrogenatmosphere, followedbydropwiseadditionofanaqueoussolutionof2MNH3 intotheflaskuntiltheblackprecipitateappeared.Thetemperature waskeptconstantat80◦C.After4hreaction,Fe3O4nanoparticles werecollectedbymagneticfieldseparation,washedwith deion-izedwater and acetone severaltimes and dried overnightin a vacuumovenat40◦C
2.1.2 SynthesisofFe3O4/poly(St-co-AA)ferrofluids Ferrofluids were synthesized by dispersion polymerization withoutorwithFe3O4magneticparticleascoreandpoly(St-co-AA)
asshellcorrespondingtoexsituandinsitucappingmethod, respec-tively.Intheexsitucappingprotocol,20mlofStandAA(St/AA variedfrom1/1to1/9)wasaddedinthreeneckflaskcontaining
200mlofwater,undernitrogenatmosphere,withvigorous stir-ring(700rpm)andtemperature(70◦C),followedbyadding0.1g
of(NH4)2S2O8,servingastheinitiator.After1hreaction,water andunreactedmonomerswereremovedbyvacuumevaporation
togetpurepoly(St-co-AA).In differencefromex situ,in insitu process, Fe3O4 capping was carried out simultaneously during thedispersioncopolymerization.Conjugatingabilityof carboxy-latedFe3O4/poly(St-co-AA)wasverifiedbyEDCactivatedreaction withHBsAb.Theresultingcomplexwasthenseparated magnet-ically, washed carefully with 1× PBS and characterized by gel electrophoresisonminiPROTEAN3cellsystem(Bio-Rad)at40mA untiltheBromophenolbluelinereachedthelowerlimitofthegels 2.1.3 Characterizationmethods
ThephasestructureofFe3O4wasstudiedbyX-raydiffraction (SIEMENSD-5000).FieldEmissionScanningElectronMicroscope (FE-SEM) and Transmission Electron Microscope (TEM) images wasanalyzedbyHitachiS-4800andJEM-1200EX(voltage:80kV, magnification:100,000×),respectively.Dynamiclightscattering (DLS)wasanalyzedwithZetasizer2000instrument(Malvern,UK) Themagneticpropertiesofpowderandferrofluidweremeasured withhomemadevibratingsamplemagnetometer(VSM),Quantum DesignPhysicalPropertiesMeasurementSystem(PPMS), respec-tively and were evaluated in term of saturationmagnetization andcoercivity Themolecularstructureof Fe O /poly(St-co-AA)
Trang 3Fig 1.Heating experiment set-up.
wascharacterizedbyInfrared(IR)Nicolet6700FT-IR
spectrom-eter(KBrpellets,400–4000cm−1,withresolutionof4cm−1)and
ProtonNuclearMagneticResonance(1HNMR)500MHzBrucker
spectrometer
2.1.4 Magneticheatingexperiment
In thisexperiment a generator(RDOHFI 5kW) wasusedto
createanalternatingmagneticfield ofamplitudefrom40Oeto
100Oeatfrequencyof236kHz(Fig.1).Samplesweredispersed
in0.09–0.9mlofwaterandkeptinaround-bottom-shapedglass
holder Temperature variation range of -20–250◦C or 0–200◦C
was measured online either by optical thermometer(Opsens)
orCopper-Constantanthermocouple,respectively.Themeasured
periodlastsfrom20to30min
Sarcoma180cellswerecollectedfromSwissmicebearing10
daysofSarcoma180ascite.Cellsthenwerewashedthreetimes
with1×PBSandcentrifugedtoapellet.Magneticfluidwasadded
tothecancercells.Cellviabilitywasdeterminedbytrypanblue,
accordingtothestandardprocedure,describedelsewhere[12]
3 Results and discussions
3.1 Characterizationofnon-encapsulatedFe3O4and
Fe3O4/poly(St-co-AA)ferrofluids
TheinfluenceofAA onthecopolymericformationand
mor-phologywasinvestigated.Itisworthnotingthatthefunctionof
carboxylicacidin AAmonomer ismultiple: first,itinducesthe
formationofpolymerparticles,therebyincreasingthe
polymeriza-tionrate;second,itstabilizesthegrowingparticlesandfinally,it
providesreactivesitesforbiomolecularbinding(e.g.,withtheaim
forsandwich-typeimmunoassaydetectionofhepatitisBAntigene
(HBsAg),hepatitisBsurfaceantibody(HBsAb)shouldbeusedasa
probe).Thus,inthisstudy,differentratiosofSt/AA(from1/1to1/9)
werepreliminarilytested.ToquantitativelyestimateCOOH
den-sity,availableforproteinbindingonthesurfaces,XPSareusually
requiredandwillnotbereportedinthispaper.However,FE-SEM
imagesshowedthattherewasalmostnosignificantdifferencein
morphologyinsuchbroadratio(St/AA)range.Forfurther
investi-gation,therationofSt/AAas1/9wasrationalizedformaximizing
numberofbindingsitesforbiomolecularconjugation
Next,quite strongdiffractionlines in XRDpattern indicated
thatFe3O4particleshavebeenwellcrystallized(Fig.S1,
support-inginformation).SixcharacteristicpeaksforFe3O4corresponding
to(220),(311),(400),(422),(511)and(440)wereobservedin
uncappednanoFe3O4particles(JCPDSfilePDFno.65-3107).On
thebasicofSherrer’sformulacrystallinesizeDwascalculatedand
furtherconfirmedbytheTEManalysis.Briefly,XRD,TEMand
FE-SEManalysesindicatedthatFe3O4particleshadasphericalshape,
asmoothsurfacemorphologyandestimatedparticlesizeof20nm (Fig.2A).AlthoughnotbeingfullyinvestigatedbyTEMtechniques, carefulimagingatefficientlyhighmagnification(FE-SEM)can pro-videa goodevaluationaboutparticlesizeand morphology.The cappingprocesswhichassociatedwiththeformationof cumber-somepoly(St-co-AA)onthesurfaceofFe3O4leadstoasignificant increaseinsizeofcore–shellnanosphere(50–70nm)comparedto thatofnakedFe3O4coreanditcanbeeasilyvisualizedbyFE-SEM imagesinFig.2B.DLSdatacorrelatedsatisfactorilywithFE-SEM resultsand alsoindicatedthattheparticlesizedistributionwas relativelynarrow(Fig.2C).ThediscrepancybetweenFE-SEMand DLSdatacanbeunderstoodiftakingintoaccountthefactthat FE-SEMimagesaretakeninadriedstatewhileDLSexperimentwas carriedoutinsolution
BycomparisonofIRspectraofAA,St,bulkFe3O4(figuresnot shown) and Fe3O4/poly(St-co-AA) (Fig 3A) it can be seen that poly(St-co-AA)hassummarizedallcharacteristicbandsofbothSt andAAunits.OnthespectrumofFe3O4/poly(St-co-AA),the pres-enceoffreecarboxylgrouponthesurfacewasconfirmedfromthe
C Ostretchingband(1702cm−1)aswellasaplateauofOH stretch-ingbandatca.3015cm−1.Theoriginofthisplateaucouldbealso assignedtoC–Hstretchingofbenzenering,whichinitiallyappeared
at3030cm−1inStunit.ItcanbealsoinferredthatCOOHwasatthe surfaceandthecoreisrichinStwhiletheshellisrichinAA.This featureisveryimportantforeffectiveconjugationofbiomolecules
onmagneticNPsurface
Next,theupshiftingofcharacteristicabsorptionofFe–Obonding from575cm−1 inbulkFe3O4 [13]to652cm−1inFe3O4 /poly(St-co-AA)couldbringastrongevidencetonanosizeofFe3O4particles
inthefluids,becauseitcouldbearesultofsplittingintoalarger numberofbondsandrearranginginlocalizedelectronsofsurface atomsofFe3O4NPs[14].Also,consideringpositionshiftsofsome characteristicprotons,providedby1HNMRspectraofSt,AA,and poly(St-co-AA), polymericencapsulation mechanism wasbetter understood.MoredetailsweregiveninTableS1andFig.S2of sup-portinginformation
Further,theconjugationofHBsAbtoFe3O4/poly(St-co-AA) sur-faceviacovalentbindingbetween–NH2 and–COOHmoietiesof HBsAband Fe3O4/poly(St-co-AA), respectively, wasclearly con-firmedbydisappearanceoftheC Ostretchingband(1702cm−1)
ofcarboxylfunctionalgrouponFe3O4/poly(St-co-AA)and appear-anceofnewbandsat1681and1100cm−1,duetoC OandC–N stretchingpatterns,respectively,ofthesecondaryamidelinkage Thesefingerprintpatternsunambiguouslysignifiedthatthe con-jugationofHBsAbtoFe3O4/poly(St-co-AA)successfullytookplace
bythecovalentbindingwithamidelinkageformation(Fig.3Band Table1)[15,16].SuccessfulcovalentbindingofHBsAbontoEDC
Trang 4Fig 2. (A) FE-SEM (top) and TEM (bottom) images of naked Fe 3 O 4 powder (B) FE-SEM image of Fe 3 O 4 /poly(St-co-AA) ferrofluid with different ratios of St/AA (C) DLS size distribution of Fe 3 O 4 /poly(St-co-AA) ferrofluid (St/AA = 1/9).
Trang 54000 350 0 300 0 250 0 200 0 1500 100 0 500
AA
650
2000 180 0 160 0 140 0 120 0 1000 80 0
-0.05
0.00
0.05
0.10
0.15
0.20
0.25
1103 1681
1702
A
B
Fig 3.(A) IR spectrum of Fe 3 O 4 /poly(St-co-AA) ferrofluid (B) IR spectra of
Fe 3 O 4 /poly(St-co-AA) + HBsAb conjugate in the fingerprint region.
activatedFe3O4/poly(St-co-AA)ferrofluidswasalsoconfirmedby
gelelectrophoresis(Fig.S3,supportinginformation)
3.2 MagneticstudyofFe3O4/poly(St-co-AA)ferrofluids
The magnetic hysteresis loop, characterizing the response
ability (magnetization,M) ofmagnetic materialstoan external
magneticfield(denotedbythemagneticfieldstrength,H),
pro-videsthemainmagneticparametersofthematerials,whichare
saturation magnetization(Ms, it reflects the magnetizability of
magneticmaterials),coerciveforce(Hc,itcharacterizestheability
ofmagneticmaterialstoretainmagnetizationwhentheexternal
magneticfieldisremoved)andmagneticremanence(Mr,itreflects
Fig 4. PPMS- magnetization curve of different Fe 3 O 4 /poly(St-co-AA) ferrofluids (St/AA = 1/9).
theremainingmagnetizationofmagneticmaterialswhenan exter-nalmagneticfieldisremoved).Thesuperparamagneticproperty (responsetoexternalappliedmagneticfieldwithoutretainingany magnetismafterremovalofthemagneticfield)ofFe3O4NPswas documented by the hysteresis loop with almost immeasurable coercivity(afewofOe).Frommagnetizationcurve,takenatroom temperature(300K)fornakedFe3O4NPs(Fig.S4,supporting infor-mation)thesaturationmagnetizationforFe3O4NPsisestimatedas
ca.70emu/g,slightlylowerthanthatofbulkFe3O4(ca.90emu/g) ThisdiscrepancyinMscanberesultedfromthedifferenceof par-ticlesizeand/orsurfacemodificationprocessesasitwaswidely reportedintheliterature[17–22]
ThesaturationmagnetizationofFe3O4/poly(St-co-AA)fluidwas showninFig.4.Asobserved,underthesameexperimental con-ditionsthefluid magnetizationraisedremarkably,from0.09 to 0.20emu/gwhencappingmethodwaschangedaccordinglyfrom
exsitutoinsitu.Further,byusinghighpowerultrasonicdispersion
ofFe3O4NPsduring30minbeforecapping,Fe3O4/poly(St-co-AA) ferrofluidswithrelativelyhighmagnetizationof0.65emu/gcould
beobtained(denotedasFe3O4/poly(St-co-AA)is-opt,Fig.4).Itwas establishedthatthelinearinterpolationbetweensaturation mag-netizationofFe3O4 nanoparticlesandferrofluidcouldbeusedto calculatethecontentofFe3O4 in thelater (Table2).Effectively, sinceFe3O4NPsandFe3O4/poly(St-co-AA)ferrofluidshave satu-rationmagnetizationof70emu/gand0.65emu/g,respectively,it canbeinferredthattheferrofluidscontain0.9286wt%ofFe3O4NPs, correspondingto9.286mgFe3O4pergramofferrofluidsolution
It iswellknownthatthestability ofmagnetic NPsisa crit-ical issue to be controlled, since Van der Waals’ forces and magneticdipole–dipoleinteractionsgeneratedfromresidual mag-netic moments tend to make the particles agglomerated and flocculated.In oursystem,the presenceof poly(St-co-AA)shell
on the surface of Fe3O4 NPs was expected to increase
stabil-Table 1
Main IR characteristic bands of St, AA, Fe 3 O 4 , Fe 3 O 4 /poly(St-co-AA) and Fe 3 O 4 /poly(St-co-AA) + HBsAb conjugate.
Possible assignments/ (cm−1) AA [14] St [14] Bulk Fe 3 O 4 [12] Nano Fe 3 O 4 Fe 3 O 4 /poly(St-co-AA) Fe 3 O 4 /poly(St-co-AA) + HBsAb
Trang 6theparticles areagglomeratedorflocculated,otherdirect
tech-niquessuchassmallangleX-rayand/orneutronscatteringshould
beappliedtomakesurethatthestabilityofthesynthesized
fer-rofluidwashigh
3.3 MagneticheatingofFe3O4/poly(St-co-AA)ferrofluids
Asdiscussedabove,NPsmustbeplacedunderanalternating
magneticfieldfora certainperiod oftimesinordertoincrease
temperatureto42–46◦C.Asthetimeperiodgetslonger,the
nor-maltissuessurroundingtumortissueswillgetmoredamages,so
reducedheatingtime,equivalenttoincreasedinitialslopeof
heat-ingcurve(orSLP)isrequired.ForFe3O4/poly(St-co-AA)ferrofluids,
heatingcurvesmeasuredatfixedfieldstrength(60Oeand236kHz)
withdifferentconcentrationsofFe3O4NPs(0.1–1mg/ml)were
rep-resentedinFig.6A.Theseheatingcurvesclearlydemonstratedthat
afteraperiodoftimeofabout25min.(1400s)theferrofluid
tem-peraturetendstosaturatedatsomecharacteristictemperatureTs,
asindicated in Table3.From this table, thelinear dependence
Fig 5. Magnetic stability of the optimized Fe 3 O 4 /poly(St-co-AA) ferrofluid
(St/AA = 1/9).
Table 3
Saturation temperature T s , T and dT/dt of Fe 3 O 4 /poly(St-co-AA) ferrofluid at
dif-ferent values of Fe 3 O 4 concentration.
Fe concentration
(mg/ml)
dT/dt ( ◦ C/s) T s ( ◦ C) T = T s − T r ( ◦ C) SLP (kW/g)
1 0.12 79.5 49.5 0.5
0.7 0.073 67.1 37.1 0.43
0.5 0.046 57 27 0.38
0.3 0.042 48.6 28.6 0.58
0.1 0.022 44.2 24.2 0.92
Ontheoneside,themoretheamountofthemagneticNPsor thestrongermagneticfield(Fig.6B),themoretheheatcouldbe generatedandthehighertemperaturecouldbereached.However,
itshouldbeawarethatmagneticNPdose,appliedtothetumor regionshouldbeaslowaspossibleinordertoreducethetoxicity Forabovediscussedreasons,theconcentrationandmagneticfield strengthshouldbeoptimized.AsindicatedinTable4,atfrequency
of236kHzandFe3O4concentrationof0.5mg/mlthetemperature riseofFe3O4/poly(St-co-AA)ferrofluidexhibitsthehighestvalue (43.5◦C)forthefieldstrengthrangeof40–80Oe
30 40 50 60 70 80
Fe 3 O 4/poly(St-co-AA)-is-op t
t (s)
(1 mg/ml) (0.7 mg/ml) (0.5 mg/ml) (0.3 mg/ml) (0.1 mg/ml)
0
30 40 50 60 70 80 90 100
oC)
oC)
t (s)
Fig 6.(A) Heating curves of Fe 3 O 4 /poly(St-co-AA) ferrofluid at different values of
Fe 3 O 4 concentration (B) Heating curves of Fe 3 O 4 /poly(St-co-AA) ferrofluid at
Trang 7dif-0 1dif-0 2dif-0 30 40 50 60
0
20
40
60
80
100
time (minutes)
Fig 7.Ex vivo heating experiment with Sacoma 180 cells performed for ferrofluid
concentration of 0.4 mg/ml.
Under these optimized conditions,ex vivo magnetic heating
experimentwasperformedonSarcoma180cancercells.Itcanbe
observedthatintheabsenceofACfieldthecellcouldsurvivefor
over72h[12],whileasillustratedinFig.7,thepresenceof
fer-rofluidsignificantlyinhibitedmorethan50%ofcancercellsafter
ca.20minandtotallykilledthemafter70–80min.Althoughbeing
preliminary,theresultsarepromising.Furtherexperimentswillbe
completedforsearchingoptimalconditionsforreal,clinic
hyper-thermictreatment
Next,itcanbeeasilyseenfromFig.8thatSLPstrictlyfollowed
square dependence onthefield amplitude H,exhibiting
super-paramagneticandsingledomainbehaviorofmagneticNPsinthe
Table 4
Saturation temperature T s , T and dT/dt of Fe 3 O 4 /poly(St-co-AA) ferrofluid at
dif-ferent values of magnetic field strength.
Fe concentration
(mg/ml)
H (Oe) dT/dt ( ◦ C/s) T s ( ◦ C) T = T s − T r ( ◦ C) SLP (kW/g)
0.5 80 0.1 73.5 43.5 0.84
70 0.065 67.8 37.8 0.54
60 0.046 57 27 0.38
50 0.034 47 17 0.28
40 0.017 37.6 7.6 0.14
0.02
0.04
0.06
0.08
0.10
o C/s)
H2 (102 Oe)
Fig 8.Linear dependence of dT/dt on the square amplitude of the magnetic field H 2
Table 5
Comparison of main magnetic heating parameters with Ref [25]
Parameters This study Ref [25]
Magnetic ferrofluid Fe 3 O 4 /poly(St-co-AA) Fe 3 O 4 /chitosan
AC field parameters H = 4.8 kA/m (60 Oe) H = 30 kA/m (377 Oe)
Q = (H,f) = 1.13 10 9 (A/ms) Q = (H,f) = 2.4 10 9 (A/ms) Ferrofluid concentration ≤0.5 mg/ml 20 mg/ml
Saturation temperature 44–57◦C 53.7◦C
ferrofluid Performingheating experiment atfixedfrequency of
f=236kHzandvariedmagneticfieldstrengthfrom60to100Oe andmeasuringthehysteresisareas,S,alineardependenceof calcu-latedSLPonthehysteresisareacanbeinferred(figurenotshown) Thisfindingsuggeststhat thelosspower comesbothfrom the Néelrelaxationprocesswithsignificantcontributionofthe hystere-sismechanism[23].ItshouldbeemphasizedthatSLPdataofour investigatedsamplesvaryquitebroadly:from0.14upto0.84kW/g correspondingto40Oeand80Oe,respectively(Table4).Itshould keepinmindthatSLPvaluesalsodependonparticlesizeandthat parameternormallyvariesfromonetoanotherindifferentstudies However,tothebestofourknowledge,underthe“quasi-similar” conditions,thefoundvaluesofSLParesuperiororatleast com-parabletothebestresults,recentlyreportedbyHergtandTimko, respectivelyinRefs.[10,24].Furthermore,underthoseoptimized
ACfiledconditions,theferrofluidexhibitedhighlyefficientandeasy controllablemagneticheatingeffectforhypertherimiaatmuchless
Fe3O4dose,withrespecttoearlierreportedstudiesofZhaoetal [25],althoughnotthesamepolymericshellwasused(Table5) Theseresultsareverypromisingforfurtherinvivohyperthermic applications
Besidestheabovemain discussedparameters(concentration and magnetic field strength), there are other parameters that may affect magnetic heating such as particle size, coercivity, remanence but theywereintensively studiedin many other reports[26–29]andwillnotberepeatedinthisstudy.Nevertheless,
itmightworthnotingthatunderthesameexperimental condi-tionsexceptforSt/AAratio,thedependenceofTonthisratio wasobservedandplottedinFig.9.Effectively,St/AAratiovariation probablyrelatedtotheviscositychangeofFe3O4/poly(St-co-AA) ferrofluids.ItiswellknownthattheheatdissipatedthroughNéel
30 40 50 60 70 80 90 100 110
o C)
t (s)
1600
Fig 9.Heating curves of Fe 3 O 4 /poly(St-co-AA) ferrofluid at different values of St/AA
Trang 8tionalization of carboxylated Fe3O4 magnetic NPs to obtain
Fe3O4/poly(St-co-AA) ferrofluids was developed Owingto
car-boxylatedgroups, Fe3O4/poly(St-co-AA) canbe usedin
biocon-jugation reaction A correlating discussion has been given on
dependence of magnetic heating effect on ACfield parameters
andFe3O4 concentration.The obtainedfluid exhibitsmore
effi-cientandtunablemagneticheatingeffectforhyperthermiaatmuch
lessFe3O4concentration,withrespecttoearlierreportedresults
Nevertheless,furtherstudiesonfluidstability, heatingrate
effi-ciency(timeexposure,Fe3O4dose,ACfieldparameters,toxicity)
andinvivoexperimentsshouldbecontinuedandwillbereported
intheupcomingpaper
Acknowledgements
Theauthorsaregratefulforthefinancialsupportforthiswork
byMOSTapplicationorientedbasicresearchproject(2009–2012,
code:04/02/742/2009/HÐ-ÐTÐL)andVASTkeyprojecton
applica-tionofferrofluid(2009–2010)
Supplementarydataassociatedwiththisarticlecanbefound,in
theonlineversion,atdoi:10.1016/j.colsurfa.2011.02.050
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