基于磷酸化修饰的核_壳硅纳米颗粒药物缓释体研究

Vo.l30高等学校化学学报No.220092CHEMICALJOURNALOFCHINESEUNIVERSITIES283~288/何晓晓,海罗,王柯敏,伍旭,谭蔚泓(,,,,,410082)(PYM)/(PYMPO4SiNP),PYMPO4SiNP.,,PYMPO4SiNP,PYM,.,PYMPO4SiNP,72%3781%,CNE2,CNE2,/PO4SiNP./.;;;O657A02510790(2009)02028306:20080919.:(:2002CB51310010)(:2003BA310A16)(:107084)(:NCET060697)(:90606003,20775021)(:06JJ10004).:,,,,,.Emai:[e-mail],,[1].,[2],[3~6]:(1),,;(2),,;(3),,;(4).,[7].,,[8][9,10][11]DNA[12].,,,,[13,14].,(MSNs),,Lai[15]MSNsCdS,Mal[16]MSNs,.,MSNspH[17][18,19][20].,.,.,/.(PYM),TritonX100PYM,TEOSPYM,/(PYMPO4SiNP).PYMPO4SiNP,PYMPO4SiNP.11.1(PYM!HC,l,PYM);(3Trihydroxysilylpropylmethylphosphonate,THPMP,Gelta);.CNE2,(18M).(JEM3010,);Zetasizer(3000HS,Malvern);(DU800,Beckman);(BenchmarkPlus,BioRad);(Nu4750E,Nuair).1.21.2.1PYM磷酸化核/壳硅纳米颗粒的制备[21]/(PYMSiNP).:TritonX100,480L10mg/mLPYM,30min,100L100LTEOS,24h.[22]PYMSiNP,24hPYMSiNPTHPMP,24h,,.PYM/PYM,15,30,60,90120L5PYM/(PYMPO4SiNP).1.2.2不同量磷酸硅烷化试剂制备的PYMPO4SiNP表征PYM/(PYMSiNP)PYM/(PYMPO4SiNP),10min,(TEM).PYMPO4SiNP,PYMPO4SiNP.1.2.3不同量磷酸硅烷化试剂制备的PYMPO4SiNP的PYM释放行为考察PYMPO4SiNP1mLPBS(pH74),,37∀,100r/min,9mLPBS(pH74).200L,200LPBS.PYM,290nm.PYMPO4SiNP.3,PYMPO4SiNP.1.2.4PYMPO4SiNP性能考察TEMPYM,PYM/,.(1)PYMPO4SiNP.PYMPO4SiNP,Zetasizer10dPYM/.(2)PYMPO4SiNP.PYM,,PYM,.284高等学校化学学报Vo.l30,:8mgPYMPO4SiNP,8mL01mol/LNaOH24h,,PYM,PYM/.3.(%)=(/)#100%(%)=(/)#100%(3)PYMPO4SiNP.PYMPO4SiNP,CNE2,025%,300096,37∀5%CO212h.PYMPO4SiNPPBS(pH74),200g/mLCNE296,37∀5%CO21,3,6,24,4872h,MTT,/(PO4SiNP),CNE2.3.22.1PYMPO4SiNPPYMSiNP15,30,60,90120LPYMPO4SiNP,1.,PYMSiNP,15,3060LPYMPO4SiNP,.,,PYMSiNP,PYMSiNP(45∃5)nm,15,3060LPYMPO4SiNP(51∃4),(44∃4)(47∃5)nm.,,PYMPO4SiNP,120L,PYMPO4SiNP,PYMSiNP,PYMPO4SiNP.Fig.1TEMimagesofPYMPO4SiNPmodifiedwithTHPMPV(THPMP)/L:(A)0;(B)15;(C)30;(D)60;(E)90;(F)120.2.2PYMPO4SiNPPYMSiNP15,30,6090LPYMPO4SiNP2,-124,-239,-308,-453-483mV.,PYMPO4SiNP,,,..285No.2何晓晓等:基于磷酸化修饰的核/壳硅纳米颗粒药物缓释体研究Fig.2potentialofPYMPO4SiNPmodifiedwithTHPMPV(THPMP)/L:a.0;b.15;c.30;d.60;e.90.Fig.3DrugreleasebehaviorofPYMPO4SiNPmodifiedwith15L(a),30L(b),60L(c),90L(d)THPMPandfreePYM(e)2.3PYMPO4SiNPPYM15,30,6090LPYMPO4SiNPPYM,PYM.PYMPO4SiNPPBS(pH74),PYM,,3.,PYM6h95%,PYMPO4SiNP,PYM:6h,PYM,,PYM;7~168h,,PYM.,.4PYMPO4SiNP,PYM.15LPYMPO4SiNP30%,;30LPYMPO4SiNP45%,;60LPYMPO4SiNP50%,,75%24h,;90LPYMPO4SiNP48h,.,30LPYM,.2.430LPYMPO4SiNP2.4.1PYMPO4SiNP的稳定性,..,.PYMPO4SiNP,4,,30LPYMPO4SiNP10d,,70nm,PYMPO4SiNP,.,,,,[23,24].2.4.2PYMPO4SiNP的载药量和包封率PYM,.,:y=00109x-00013,R=09997.,PYM,PYM.,PYMPO4SiNP72%3781%.2.4.3PYMPO4SiNP的抑癌活性5CNE2(PO4SiNP)286高等学校化学学报Vo.l30Fig.4HydrodynamicsizevarietyofPYMPO4SiNPmodifiedwith30LTHPMPinwatersuspensionFig.5SurvivalrateofCNE2cellsafterincubationwith200g/mLPO4SiNP(a)andPYMPO4SiNP(b)fordifferenttime(PYMPO4SiNP).30L,PO4SiNPPYM,PYMPO4SiNPPYM.,CNE2PYMPO4SiNP,,,,72h17%;PO4SiNP72hCNE2,90%.,PYMPO4SiNP,,PO4SiNP.,,,/(PYMPO4SiNP).,,,;,,.[1]EvonneM.R.,DavidR.K.,JanelleL.F.,etal..J.Am.Chem.Soc.[J],2007,129(16):4961%4972[2]TanW.H.,WangK.M.,HeX.X.,etal..Med.Res.Rev.[J],2004,24(5):621%638[3]MacoulK.L.,PavanLangstonD..ArchOphthalmol(Chic)[J],1975,93:587%590[4]QuigleyH.A.,PollackI.P.,HarbinT.,etal..ArchOphthalmol(Chic)[J],1975,93:771%775[5]SanbornG.E.,AnandR.,TortiR.E.,etal..ArchOphthalmol(Chic)[J],1992,110:188%195[6]SmithT.J.,PearsonP.A.,HollinsJ.L.,etal..ArchOphthalmol(Chic)[J],1992,110:255%258[7]LIXinWei(),SUNLiXin(),LINXiaoHong(),etal..ProgressinChemistry()[J],2007,19(1):87%92[8]YangH.H.,ZhangS.Q.,ChenX.L.,etal..Ana.lChem.[J],2004,76(5):1316%1321[9]HerrJ.K.,SmithJ.E.,MedleyC.D.,etal..Ana.lChem.[J],2006,78(9):2918%2924[10]XINGXinLi(),HEXiaoXiao(),WANGKeMin(),etal..Chem.J.ChineseUniversities()[J],2006,27(11):2076%2078[11]WangL.,ZhaoW.,O&DonoghueM.B.,etal..BioconjugateChem.[J],2007,18(2):297%301[12]ZhaoX.J.,RovelynT.,TanW.H..J.Am.Chem.Soc.[J],2003,125(38):11474%11475[13]HEXiaoXiao(),WANGKeMin(),TANWeiHong(),etal..ChineseSc.iBul.l()[J],2002,47(18):1365%1369[14]LiuY.Y.,MiyoshiH.,NakamuraM.,etal..ColloidsandSurfacesB:Biointerfaces[J],2007,58:180%187[15]LaiC.Y.,TrewynB.G.,JeftinijaD.M.,etal..J.Am.Chem.Soc.[J],2003,125(15):4451%4459[16]MalN.K.,FujiwaraM.,TanakaY..Nature[J],2003,421(23):350%353[17]NguyenT.D.,KenC.F.,LiongM.,etal..Org.Lett.[J],2006,8(15):3363%3366[18]NguyenT.D.,LiuY.,SahaS.,etal..J.Am.Chem.Soc.[J],2007,129(3):626%634[19]NguyenT.D.,TsengH.R.,CelestreP.C.,etal..Proc.Nat.lAcad.Sc.iUSA[J],2005,102(29):10029%10034[20]KenC.F.,NguyenT.D.,StoddartJ.F..Chem.Mater.[J],2006,18(25):5919%5928[21]HEXiaoXiao(),CHENJiYun(),WANGKeMin(),etal..Chem.J.ChineseUniversities(287No.2何晓晓等:基于磷酸化修饰的核/壳硅纳米颗粒药物缓释体研究)[J],2006,27(10):1835%1839[22]NIEHaiLong(),HEXiaoXiao(),HUOXiQin(),etal..Chem.J.ChineseUniversities()[J],2008,29(3):477%481[23]LuJ.,LiongM.,ZinkJ.I.,etal..Small[J],2007,3(8):1341%1346[24]BagweR.P.,HilliardL.R.,TanW.H..Langmuir[J],2006,22(9):4357%4362NovelDrugCarrierSystemBasedonPhosphonateterminatedCore/shellSilicaNanoparticlesHEXiaoXiao,HAILuo,WANGKeMin*,WUXu,TANWeiHong(BiomedicalEngineeringCenter,StateKeyLaboratoryofChemo/BiosensingandChemometrics,CollegeofChemistryandChemicalEngineering,HunanUniversity,KeyLaboratoryforBioNano