酸敏感靶向的阿霉素聚酰胺-胺型树枝状高分子的抗肿瘤研究-论文.pdf

《酸敏感靶向的阿霉素聚酰胺-胺型树枝状高分子的抗肿瘤研究-论文.pdf》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。

1、JournalofChinesePharmaceuticalSciencesht~：／／www．jcpslaeicnAcidsensitivedoxorubicin-PAMAMwithtumortargetingprofileFeiPeng，PengchaoGao，XiangtaoWang，XinHu，．SchoolofPharmaceuticalSciences,PekingUniversityHealthScienceCenter,Beij'ing100191，China2．ChineseAcademyofMe~calSciencesandPekingUnionMeSca

2、lCollege,InstituteofMedicinalPlantDevelopment,Beijing100094,ChinaAbstract：Poly(amidoamine)dendrimersareemergingasversatileandderivatizablenano-scaledrugdeliveryvehicles．Inourstudy．cis．4，7，l0，13，16，19一docosahexenoicacidanddoxombicinwereconjugatedtogeneration2．5PAMAM．Themoleculararchitectureo

3、fthecarrierwasdesignedforoptimizedbloodcirculationandoptimizeddrugreleasethroughtheuseofpH-sensitivehydrazonelinkages．Invitro．DHA．PAMAM—DOXconjugateswereabletoreleasetwiceasmuchdoxorubicinatpH4．5(1ysosomalpH)asatpH7．4．ensuringmorepronouncedantitumoractivity．UponintravenousadministrationtoIC

4、Rmice，theDHA．PAMAM—DOXdeliverysystemsresultedinmoreplasmaexposureofdoxombicinthanfreedoxombicinsolution．IneficacystudiesperformedwithB6D2F1micebearingB16melanomatumors．DHA．PAMAM—DOXwassignificantlymoree衔cientininhibitingtumorgrowththanfreedoxorubicinatthedoseequivalentto5mg／kgdoxorubicin．Ou

5、rresearchprovidesevidencethatDHA-PAMAM—DOXconjugateshavethepotentialtoenhancetheeffectofcancertherapyinthecourseofdeliveringanticancerdrugstotheirtargetsites．Keywords：PAMAM：Doxorubicin；Docosahexenoicacid；AntitumortreatmentCLCnumber：R969Documentcode：AArticleID：1003—1057(2013)1—81-081．Intr0du

6、cti0n(PUFAs)，asbiochemicalprecursors．OnetypeofPUFAsiscis-4，7，10，13，16，19一docosahexenoicacids(DHAs，targetingSmal1．moleculecancerchemotherapyiscommonlymolecule)，whichcanbindtofattyacidreceptors，includinglimitedbyalackofspecificityintargetingtotumorG．proteincoupledreceptors．onthecancercells【一．

7、tissuesanddose—limitingtoxicitiescausedbydrugTherefore．DHAswereusedastargetingmoietiesinprevi—exposuretonon-targettissues．Inrecentyears，however，OUSresearchtoincreasetheamountofPAMAMfG2．5)adiverserangeofcarriershavebeendevelopedtoaccumulatinginthetumor．In