共聚物胶束递送抗肿瘤药物逆转乳腺癌细胞耐药性的研究

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1、Overcomingdrug-resistancewithcopolymermicellesindeliveringanti-cancerdrugtobreasttumorcells.#MinHan*510152025303540(collegeofpharmaceuticalsciences,Zhejianguniversity,HangZhou310058)Abstract:Drugresistanceisoneofthecriticalreasonsleadingtofailureinchemotherapy.Wedevel

2、opedPEG-PCLpolymermicelleencapsulatingDoxorubicin(DOX)asanoveldrugdeliverysystemtoinhibitthedrug-resistanceofadriamycin-resistantK562tumorcells(K562/ADR)inpresentstudy,andthephysico-chemicalpropertiesofthemicelles,accumulationandcytotoxicityofDOXinK562/ADRcellswerefurth

3、erstudied.ThemicellesloadingDOXwerepreparedbysolventevaporationmethodwithadiameterof36nmandaZetapotentialof13.8mV.TheentrapmentefficiencyofDOXwas(48.6±2.3)%.Themicellesshowedsustainedrelease,andincreaseduptakeandcellularcytotoxicityaswellasdecreasedeffluxofDOXinK562/ADR

4、cells.ThisstudysuggestedthatPEG-PCLmicellespossessapotentialprospectinreversingthemultidrugresistanceofthetumorcells.Keywords:doxorubicin;PEG-PCL;breasttumorcells0IntroductionCancerisoneoftheleadingcausesofmorbidityandaccountsforaquarterofalldeathsaroundtheworld.Chemoth

5、erapyisoneofthemostcommonlyusedtreatmentsforcancer,butchemotherapyresistanceoftenlimitsitseffect.Oneofthemostfrequentphenotypeofmultidrugresistance(MDR)istheoverexpressionofp-glycoprotein(Pgp)intumorcells,a170-kDaMDR1geneproduct1-3.Pgpcanactivelypumpoutitssubstratesthat

6、resultsinreducedintracellularaccumulationofcertaindrugsanddecreasedtherapeuticefficacy.Hitherto,oneapproachtoincreasedrugaccumulationincellsistoenvelopedrugintonano-scalevehiclestoescapetherecognitionbyPgp.Micellesformedbyamphiphilicblockcopolymershaveattractedsignifica

7、ntattentioninmedicalfieldsduetotheirvariousadvantagesindrugdeliveryapplications4,whichincludeenhancedsolubilization5,stabilization,anddeliveryofchallengingagents6,7.Polymericmicellescouldaccommodateanti-tumordrugsintheirhydrophobiccoreandthusexceedthesolubilitylimitofhy

8、drophobicdrugs8.Furthermore,thehydrophiliccoronaofmicellesprovidesastabilizinginterfacebetweentheirinnercorean