基于低分子量聚乙烯亚胺和油酸的负电性基因载体.pdf

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1、物理化学学~E(WuliHuaxueXuebao)FebruaryActa．一Chim．Sin．2014，30(2)，345—350345[Article]doi：10．3866／PKU．WHXB201311282www．whxb．pku．edu．cn基于低分子量聚乙烯亚胺和油酸的负电性基因载体杨阳’郭霞，f四川大学华西医院生物治疗国家重点实验室，成都610041；扬州大学化学化工学院，江苏扬州225002)摘要：构建负电性的基因载体、发展基于低分子量聚乙烯亚胺(PEI)I~基因载体对基因传递研究具有重要意义．本文基于低分子量聚乙烯亚胺(2kDa)和油酸构建了负电性的基因载体

2、．它通过混合聚乙烯亚胺(2kDa)、dsDNA4~1]油酸胶束而自发形成．该基因载体在血清中很稳定，细胞毒性非常低，可包封80％以上DNA．通过1，2-二硬脂酰．sn．甘油．3．磷酸乙醇胺．M【甲氧基(聚乙二醇2000)]铵~(DSPE-PEG)~其表面进行修饰，发现多达90％的基因可被细胞摄取．关键词：聚乙烯亚胺：油酸：基因传递中图分类号：0648NegativelyChargedLipopolyplexforGeneDeliveryBasedonLow-Molecular-WeightPolyethylenimineandOleicAcidYANGYang’GUOXia，

3、(StateKeyLaboratoryofBiotherapy,WestChinaHospitalSichuanUniversity,Chengdu610041，R．China；SchoolofChemistryandChemicalEngineering,YangzhouUniversity,Yangzhou225002，JiangsuProvince,PR．China)Abstract：Thedevelopmentofsyntheticvectorsbasedonlow-molecular-weightpolyethylenimine(PEI)andtheconstruc

4、tionofnegativelychargedvectorswithhighnucleicacidencaDsuIatiOnaretwoofthecurrentresearchtrendsingenedelivery．1nthepresentstudy．wedevelopedastableandnegativelychargedlipopolyplexbasedonoleicacidandalow—molecular—weightPEJf2kDa)；itwasformedbysimultaneouslymixingoleicacidmicellesandapolyplexpr

5、oducedfromPEI(2kDa)andoligodsDNA．Thislipopolyplexisstableinserum，andbecauseoftheIowmolecularweightofthePEI，theIipopolyplexexhibitsverylowtoxicity．TheencaOsuIatiOnefficienciesofnucleicacidsbytraditionaIanionicvectorsareIow，butveryhigh(morethan80％)bythislipopolyplex．Suitablesurfacemodificatio

6、nwith1，2-distearoryl-sn—glycero-3一phosphoethanolamine—N-meth0xy(p0IyethyIeneglycol一2000)ammoniumsaltenabledthelipopolyplextobindtocells，andahighcellularuptakeefficiency(ca90％)wasobservedinvitro．KeyWords：Polyethylenimine；Oleicacid；Genedelivery1Introductionliveryagentsandhence，formacomplexpro

7、tectingnucleicac—cationicliposomesandpolymersarewidelyusedasnonvi—idfromdegradationbynuclease．Ta1(orsynthetic)vectorsbominvitroand加vivo．Bothplas．Polyethylenimine(PEI)hasbeenoneofthemostwidelymidDNAandsiRNAbindtocationic1iposomesandpolymersstudiedsyntheti