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1、HER-2靶向硼脂质体的细胞靶向与细胞内分布研究?3l21丝壁垦兰堕苤查生旦笙垄鲞笙塑iniolMedPmt,August2005,Vol25,No.4HER一2靶向硼脂质体的细胞靶向与细胞内分布研究郑树魏启春沈俐ErikaBohlKullbergLarsGedda【摘要】目的分析新制备的HER一2靶向硼脂质体在细胞靶向,滞留及细胞内分布等方面的特性,探讨该脂质体作为靶向给药系统用于硼中子俘获治疗研究的可能性.方法分别从靶向剂Trastuzumab,脂质体和装载的WSA3个方面观察SK—BR一3细胞对I-Trastuzumab-WSA一H一脂质体的摄取与滞留.Trastuzumab标记了I
2、用伽玛计数器检测;脂质体标记了H用液闪计数器检测;WSA用感应耦合等离子体一质谱仪检测.激光共聚焦显微镜观察WSA在细胞内的分布.结果最初8h细胞对I-Trastuzumab的摄取量快速增加,24h后细胞内I量反而有所下降.细胞对H一脂质体的摄取随培养时间而增加,直到48h也没有达到平台期.培养4,8及24h,细胞含硼量分别达到55,78及132x10～.细胞摄取I-Trastuzumab—WSA.H.脂质体后,在普通培养液中培养24和48h,分别有90%,67%的WSA滞留在细胞内.激光共聚焦显微镜下显示大部分WSA位于细胞浆.结论细胞摄取量满意,WSA在细胞内滞留时间长,说明I-Tra
3、stuzumab—WSA一H一脂质体是一个很好的运载工具,有希望应用于硼中子俘获治疗研究.【关键词】硼中子俘获治疗;脂质体;细胞靶向;细胞滞留Cellulartargetingandsubcellulardist~bufionofHER-2targetingboronfiposomesZHENGShu,WE1Qi—chun,SHENLi,eta1.CancerInstitute,ZhejiangUniversity,Hangzhou310009,ChinaCorrespondingauthor:WEIQi—chu,Emaif:weiqichun@hotmaif.con【Abstract】O
4、bjectiveToinvestigateHER一2targetingboronliposomesasapotentialdrugdeliveryvehicleforboronneutroncapturetherapy,inrespecttocellularuptake,retentionandthesubcellularlocation.MethodsCellularuptakeandretentionof125I-Trastuzumab—WSA一H—LiposomeswerestudiedusingSK—BR一3cells,withregardtothetargetingagent,c
5、arriers,andtheloadedWSA.Astherewas'IlabeledonTrastuzumabandHonliposomes.Trastuzumabandtheliposomescouldbemeasuredusingagammacounterandaliquidscintillationcounter,respectively.WSAcouldbemeasuredbyinductivelycoupledplasmamassspectrometry(ICP—MS).SubcellulardistributionofWASwasstudiedusingconfocalmic
6、roscopy.ResultsTheuptakeofIlabeledTrastuzumabreachedaplateauafter8handdeclinedafter24hincubation.ForH—Liposome,thereWasadifierentuptakepattern.i.e.,noplateauwasreachedandnodeclinewasseenevenafter48hincubation.Theboronuptakeincreasedwithprolongationofincubationtime,for4,8and24hoursincubation,itreac
7、hed55ppm,78ppm,and123ppm,respectively.Afterincubationinconventionalmediumfor24hover9O%WSAand70%oftheH—Liposomesstillremainedinthecells.whileonly35%ofthel-Trastuzumabremained.ThediFencewasevenmorepronouncedafter48
