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1、Biodegradablesynthetichigh-densitylipoproteinnanoparticlesforatherosclerosisaa,b,1SeanMarracheandShantaDharabNanoTherapeuticsResearchLaboratory,DepartmentofChemistry,andDepartmentofPhysiologyandPharmacology,UniversityofGeorgia,Athens,GA30602EditedbyRobertLanger,MassachusettsInst
2、ituteofTechnology,Cambridge,MA,andapprovedApril15,2013(receivedforreviewJanuary29,2013)Atherosclerosisremainsoneofthemostcommoncausesofdeathinanimportantroleinplaquerupture(7).AuniqueapproachfortheUnitedStatesandthroughouttheworldbecauseofthelackofthenoninvasivedetectionofapopto
3、sisinSMCsandmacro-earlydetection.Macrophageapoptosisisamajorcontributortothephagescouldbedevelopedbytargetingthecollapseofthemi-instabilityofatheroscleroticlesions.Developmentofanapoptosistochondrialmembranepotential(ΔΨm),ahallmarkofthetargetedhigh-densitylipoprotein(HDL)-mimick
4、ingnanoparticle(NP)initiatingphaseofapoptosis(8).Thus,acompletelysynthetictocarrycontrastagentsforearlydetectionofvulnerableplaquesandbiodegradableΔΨmtargetingHDLmimickingNPcontainingcontrastagentscouldbeofenormousbenefitstopatientswiththeinitiationofpreventativetherapiesthatexpl
5、oitthevascularCHD.Surprisingly,allofthereportsonusingHDLNPsforprotectiveeffectsofHDLcanbeattractiveforatherosclerosis.imagingatherosclerosisarebasedonreconstitutedHDL(rHDL)Here,wereporttheconstructionofasynthetic,biodegradable(9–11)(SIAppendix,TableS1).ParticlesbasedonrHDLuseHDL
6、-NPplatformfordetectionofvulnerableplaquesbytargetinglipoproteinsandapoA-Iextractedfromhumanplasma.Apo-thecollapseofmitochondrialmembranepotentialthatoccursdur-tentialprobleminusingrHDLNPsincludesbatch-to-batchingapoptosis.ThisHDLmimiccontainsacoreofbiodegradablevariabilitywhenl
7、ipoproteinsareisolatedfromdonorplasmapoly(lactic-co-glycolicacid),cholesteryloleate,andaphospholipidandscale-upchallenges.AcompletelysynthetictargetedHDL-bilayercoatthatisdecoratedwithtriphenylphosphonium(TPP)mimickingNPplatformthatcannavigatethroughtheinterstitialcationsfordete
8、ctionofmitochondrialmembranepotentialcol-spacep
