Synthesisandsurfaceengineeringofironoxiden

Biomaterials26(2005)3995–4021ReviewSynthesisandsurfaceengineeringofironoxidenanoparticlesforbiomedicalapplicationsAjayKumarGuptaa,
,MonaGuptabaCrusadeLaboratoriesLimited,SouthernGeneralHospital,1345GovanRoad,GlasgowG514TF,Scotland,UKbDivisionofBiochemistryandMolecularBiology,IBLS,DavidsonBuilding,UniversityofGlasgow,GlasgowG128QQ,Scotland,UKReceived3June2004;accepted18October2004Availableonline10December2004AbstractSuperparamagneticironoxidenanoparticles(SPION)withappropriatesurfacechemistryhavebeenwidelyusedexperimentallyfornumerousinvivoapplicationssuchasmagneticresonanceimagingcontrastenhancement,tissuerepair,immunoassay,detoxificationofbiologicalfluids,hyperthermia,drugdeliveryandincellseparation,etc.Allthesebiomedicalandbioengineeringapplicationsrequirethatthesenanoparticleshavehighmagnetizationvaluesandsizesmallerthan100nmwithoverallnarrowparticlesizedistribution,sothattheparticleshaveuniformphysicalandchemicalproperties.Inaddition,theseapplicationsneedspecialsurfacecoatingofthemagneticparticles,whichhastobenotonlynon-toxicandbiocompatiblebutalsoallowatargetabledeliverywithparticlelocalizationinaspecificarea.Tothisend,mostworkinthisfieldhasbeendoneinimprovingthebiocompatibilityofthematerials,butonlyafewscientificinvestigationsanddevelopmentshavebeencarriedoutinimprovingthequalityofmagneticparticles,theirsizedistribution,theirshapeandsurfaceinadditiontocharacterizingthemtogetaprotocolforthequalitycontroloftheseparticles.Natureofsurfacecoatingsandtheirsubsequentgeometricarrangementonthenanoparticlesdeterminenotonlytheoverallsizeofthecolloidbutalsoplayasignificantroleinbiokineticsandbiodistributionofnanoparticlesinthebody.Thetypesofspecificcoating,orderivatization,forthesenanoparticlesdependontheendapplicationandshouldbechosenbykeepingaparticularapplicationinmind,whetheritbeaimedatinflammationresponseoranti-canceragents.Magneticnanoparticlescanbindtodrugs,proteins,enzymes,antibodies,ornucleotidesandcanbedirectedtoanorgan,tissue,ortumourusinganexternalmagneticfieldorcanbeheatedinalternatingmagneticfieldsforuseinhyperthermia.Thisreviewdiscussesthesyntheticchemistry,fluidstabilizationandsurfacemodificationofsuperparamagneticironoxidenanoparticles,aswellastheiruseforabovebiomedicalapplications.r2004ElsevierLtd.Allrightsreserved.Keywords:Magneticnanoparticles;MRI;Drugdelivery;Surfacemodification;Hyperthermia;Celllabelling;IronoxideContents1.Introduction............................................................................39962.Synthesisofmagneticironoxidenanoparticles....................................................39973.Surfacemodificationofmagneticnanoparticlesforbiomedicalapplicationsandtheireffectonstabilityandmagnetization40003.1.Surfacemodificationwithnon-polymericorganicstabilizers......................................40013.2.Surfacemodificationwithpolymericstabilizers...............................................4002ARTICLEINPRESS:10.1016/j.biomaterials.2004.10.012
Correspondingauthor.Tel.:[phone];fax:[phone].E-mailaddress:[e-mail](A.K.Gupta).URL:ficationofbiologicalfluids..................................................40104.2.Tissuerepair.......................................................................40104.3.Drugdelivery.......................................................................40104.4.Magneticresonanceimaging............................................................40124.5.Hyperthermia.......................................................................40134.6.Magnetofection.....................................................................40145.Concludingremarksandfuturedirections.......................................................4014References.................................................................................40141.IntroductionInthelastdecade,nanotechnologyhasdevelopedtosuchanextentthatithasbecomepossibletofabricate,characterizeandspeciallytailorthefunctionalproper-tiesofnanoparticlesforbiomedicalapplicationsanddiagnostics[1–4].Asintermediatesbetweenthemole-cularandthesolidstates,inorganicnanoparticlescombinechemicalaccessibilityinsolutionwithphysicalpropertiesofthebulkphase[5].Theyarethusidealelementsfortheconstructionofnanostructuredmateri-alsanddeviseswithadjustablephysicalandchemicalproperties[1,6].Theapplicationofsmallironoxideparticlesininvitrodiagnosticshasbeenpractisedfornearly40years[7].Inthelastdecade,increasedinvest