磁性氧化铁纳米颗粒及其磁共振成像应用_乔瑞瑞

,,,1001902010-11-262011-02-18“973”(2011CB935800),(210031358109027120820102035)(010)[e-mail]，，。，，。，，。；；；R1,O69DOI10.3724/SP.J.1260.2011.00272、[1]。(magneticnanoparticlesMNPs)(magneticresonanceimagingMRI)(contrastagent)。、[2～7]。[2,4,6,7]。AdvancedMagnetics(CambridgeMAUSA)GastroMark誖(ferumoxsil)19931996“”(USFoodandDrugAdministration,FDA)Feridex誖(誖)2000Resovist誖(ferucarbotran)[8]Combidex誖(Sinerem誖)。10[7](1)。、[9~11][12][13]。、。20114274:ACTABIOPHYSICASINICAVol.27No.4Apr.2011:272-288272-288｜ACTABIOPHYSICASINICA/MiniReview5。CompoundClassifi-cationSizeSurfacemodificationT1/2IndicationDevelop-mentTradenameFerristene(OMP)SPIO3500nm(composeofcrystalbelow50nm)Sulphonatedstyrene-di-vinylbenzenecopolymerOralGastro-intestinalSaleAbdoscan誖(GE-Healthcare)Ferumoxsil(AMI-121)SPIO300nm(composeof10nmcrystal)SiloxaneOralGastro-intestinalSaleGastroMARK誖(AdvancedMagnetics);Lumirem誖(Guerbet)Ferrixan(Ferucarbo-tran,SHU555A)SPIO60nmDextran2.4~3.6hLiverSaleResovist誖(Schering);CliavistTM(Medicadoc)Ferumoxide(AMI-25,SHU555A)SPIO120~180nm80~150nmDextran2hLiverSaleFeridex誖(AdvancedMagnetics);EndoremTM(Guerbet)(SHU555C)USPIO≤20nmDextran6hAngiographyPhase1SupravistTM(Schering)Ferumoxtran-10(AMI-227,BMS-180549)USPIO20~40nmDextran24~36hLymphnode/liver,angiographyPhase3Combidex誖(AdvancedMagnetics);Sinerem誖(Guerbet)Feruglose(PEG-feron,NC100150)USPIOCoresize5~7nmTotal20nmCarbohy-dratepol-yethyleneglycolcoating;Pegylatedstarch6hLymphnode/liver,PerfusionangiographyPreclin.ClariscanTM(GE-Healthcare)VSOP-C184USPIO7nmCitrate0.6~1.3hAngiographyPreclin.1[7]Table1Listofironoxidecontrastagentscommercializedoratdifferentclinicalstages[7]T1/2(Bloodhalf-time)273ACTABIOPHYSICASINICA｜Vol.27No.4｜Apr.20112011274/MiniReviewMRI[9~11]。[11,14,15]。MR。MRI。MRI、、、。MRI、。XMRI。MRI、、。MRI[16]。()(radiofrequencyRF)。(longitudinalrelaxation)(transverserelaxation)T1T2。。MR、。(contrast)T1T2、。MR。MRMR。MR。T1T1(T1)。T1。T2。(ferromagnetic)(ferrimagnetic)(magnetization)。(magneticsusceptibility)MR。。274｜ACTABIOPHYSICASINICA/MiniReview1[5]Fig.1MRcontrasteffectsofsuperparamagneticironoxidenanoparticles[5]T2[17]T2T2(1)[5]。T2T1。T2———T1。T2(reticuloendothelialsystemRES)、、[7,18]。SPIO(smallparticleofironoxide)USPIO(ultrasmallparticleofironoxide)。SPIOUSPIO40nm40nmSPIO40nmUSPIO。USPIORESSPIO。USPIOCombidex誖SPIOFeridex誖。。[19]275ACTABIOPHYSICASINICA｜Vol.27No.4｜Apr.20112011274/MiniReview40nmRES[6]。T1T2RES。T2T1T2。、(enhancedpermeabilityandretentioneffectEPReffect)。T2(10nm)。T2()[16]。。T1T2。Gd10-4mol/L[20]10-12mol/L[21]。、[20]。SPIOUSPIO(1980～90)()USPIO、(5)MRI-PET、MRI-、MRI-PET、MRI-SPECT。[7]。。———。1925Welo[22]。。(micro-emulsion)276｜ACTABIOPHYSICASINICA/MiniReview、-(gel-sol)、(sonochemistry)(coprecipitation)。。。[23,24]。。[7]。。。。1999Alivisatos[25]。FeCuP3()110℃60℃N2300℃FeCuP330min(10±1.5)nmγ-Fe2O3(2A)。2001Hyeon[26]Fe(CO)5γ-Fe2O3。Fe(CO)5Feγ-Fe2O3(2B)。(5%)Fe(CO)54～11nm。2002Sun[27]Fe(acac)3(1,2-4nmFe3O4Fe3O4(2C)。MFe2O4(M=Fe、Mn、Co)[28]。Peng[29]Fe3O46～50nm。Hyeon[30](10g)(2D)274、287、317、330365℃5、9、12、1622nm。。Cheon[11]Fe(acac)3(metal-dopedmagnetism-engineeredironoxide,MEIO)MFe2O4(M=Mn、Fe、Co、Ni)。MnFe2O4MRI。277ACTABIOPHYSICASINICA｜Vol.27No.4｜Apr.20112011274/MiniReview32-“”Fe3O4TEM[35]5nm11nm100nmFig.3TEMimagesofwater-solubleFe3O4nano-particlesbyusing2-pyrrolidoneascoordinatingsolvent[35]Theaverageparticlesizesofthoseshownintheleft-handsideimageandright-handsideimageareof5and11nm,respectively.Thescalebarscorrespondto100nm2(A)FeCup3γ-Fe2O3TEM[25](B)Fe(CO)5γ-Fe2O3TEM[26](C)Fe(acac)3Fe3O4TEM[27](D)Fe3O4TEM[30]Fig.2(A)γ-Fe2O3nanocrystalssynthesizedbythermaldecompositionofFeCup3[25];(B)γ-Fe2O3nanocrystalssynthesizedbythermaldecompositionofFe(CO)5[26];(C)Fe3O4nanocrystalspreparedbypyrolyzingFe(acac)3[27];(D)Magneticironoxidenanocrystalspreparedbyusingironoleateasprecursor[30]200nm10nm4.77A4.11A50nm0.2μm(A)(B)(C)(D)Colvin[31]FeOOHFeOOH12.5nmFe3O4。。1)2)、。[9,32,33]。。(2-)Fe(acac)3“”Fe3O4(3)[34,35]。278｜ACTABIOPHYSICASINICA/MiniReview“”。1)Fe3O4MRI[39]。“”(5)[10,40]。。。Fe3O4[36](PEG)“”(4)[37,38]。PEGFe3O4Fe3O4PEGPEG5Fe3O4TEM[40](A)12nm(B)27nm。100nmFig.5TEMimagesofbiocompatibleFe3O4nano-particleswithsurfacereactivemoieties[40]Theaverageparticlesizesofthoseshownin(A)and(B)areof12and27nm,respectively.Thescalebarscorrespondto100nm(A)(B)(B)4(A)PEGFe3O4TEM[38](B)(C)Fig.4(A)TEMimageofbiocompatibleFe3O4nanoparticlescoatedwithPEG[38];(B)Electrondiffractionpatterns;(C)Thehistogramofparticlesizes(A)100nm(C)Particlesize(nm)Percentage(%)0.30.20.10.0691215279ACTABIOPHYSICASINICA｜Vol.27No.4｜Apr.20112011274/MiniReview2)。。N-(N-vinyl-2-pyrrolidoneNVP)Fe(acac)3“”Fe3O4[41]。NVPFe(acac)3。Fe3O4。(polyvinylpyrrolidonePVP)Fe3O4PVPpHPBS[41]。1)2)3)[30]。[10,11,30,32]。KuffersFDA1996Feridex誖(80～150nm[5])。Feridex誖Combidex誖(20～40nm)Combidex誖。Weissleder[12]Combidex誖2mm。FDAFeridex誖。、。Weissleder[42](holo-transferrin)(monocrystaliron-oxidenanoparticleMION)。Zhao[43]C2domain(SPIO)。280｜ACTABIOPHYSICASINICA/MiniReview。〔Feridex誖MION50nm(Dextran)20～40nm〕[44]、、、[45~47]。。、。Ch