Microfluidic hydrodynamic focusing synthesis of polymer-lipid nanoparticles for siRNA delivery.[2017][Oncotarget][10.18632oncotarget.18281]

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1、www.impactjournals.com/oncotarget/Oncotarget,AdvancePublications2017Microfluidichydrodynamicfocusingsynthesisofpolymer-lipidnanoparticlesforsiRNAdeliveryXueqinHuang1,2,RobertJ.Lee1,3,YuhangQi1,YujingLi1,JiahuiLu1,QingfanMeng1,LeshengTeng1andJingXie11SchoolofLifeScie

2、nces,JilinUniversity,Changchun,Jilin130023,China2DepartmentofChemistryandPharmacy,ZhuhaiCollegeofJilinUniversity,Zhuhai,Guangdong,519041,China3DivisionofPharmaceutics,CollegeofPharmacy,TheOhioStateUniversity,Columbus,Ohio43210,USACorrespondenceto:LeshengTeng,email:t

3、englesheng@jlu.edu.cnJingXie,email:xiejing@jlu.edu.cnKeywords:microfluidic,polymer,lipidnanoparticles,siRNAdelivery,cancertreatmentReceived:December12,2016Accepted:May01,2017Published:May29,2017Copyright:Huangetal.Thisisanopen-accessarticledistributedunderthetermsof

4、theCreativeCommonsAttributionLicense(CC-BY),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.ABSTRACTSmallinterferingRNAs(siRNAs)arepromisingastherapeuticsforintractablediseasessuchascancer.However,eff

5、icientandsafedeliveryofsiRNAsinvivoremainsachallenge.Polymer-lipidhybridnanoparticles(P/LNPs)havebeenevaluatedfortherapeuticdeliveryofsiRNA.Inthisstudy,amicrofluidichydrodynamicfocusing(MF)systemwasusedtoprepareP/LNPsloadedwithVEGFsiRNA.P/LNPsmadebyMFweresmallerinpa

6、rticlesizeandhadnarrowersizedistributioncomparedtoP/LNPsformedbybulkmixing(BM).MF-synthesizedP/LNPsdemonstratedlowvehiclecytotoxicityandpotenttumorcellinhibitioninvitro.Inaddition,P/LNPsproducedbythemicrofluidicchipexhibitedprolongedbloodcirculationandincreasedAUCaf

7、teri.v.injectioncomparedtofreesiRNA.Furthermore,P/LNPssynthesizedbyMFinducedgreaterdown-regulationofVEGFmRNAandproteinlevelsaswellasgreatertumorinhibitioninaxenografttumormodel.Takentogether,P/LNPspreparedbyMFhavebeenshowntobeaneffectiveandsafetherapeuticsiRNAdelive

8、rysystemforcancertreatmentbothinvitroandinvivo.INTRODUCTIONsiRNAdeliveryefficiencymaybepossibleiftheprocessofnanocomplexsynthesiscanbeopti