Construction of redox-responsive tumor targeted cisplatin nano-delivery system for effective cancer

ContentslistsavailableatScienceDirectInternationalJournalofPharmaceuticsjournalhomepage:www.elsevier.com/locate/ijpharmConstructionofredox-responsivetumortargetedcisplatinnano-deliverysystemforeffectivecancerchemotherapyYi-YangJia,Jun-JieZhang,Ya-XuanZhang,WeiWang,ChenLi,Si-YuanZhou,Bang-LeZhang⁎DepartmentofPharmaceutics,SchoolofPharmacy,FourthMilitaryMedicalUniversity,Xi’an710032,ChinaARTICLEINFOKeywords:CisplatinRedox-responsiveTumortargetedNano-deliverysystemCancerchemotherapyABSTRACTCisplatinisoneofthemostwidelyusedplatinum-basedanticancerchemotherapeuticdrugs.However,itslowsolubility,serioussideeffectsandthedevelopmentofcisplatinresistancelimititsfurtheruseintheclinic.Controllingthedeliveryandreleaseofcisplatinatthetargetedsiteefficientlyisameaningfulwaytoovercometheseundesirablesideeffectsofcisplatin.Herein,atumortargetedandstimuliresponsivenano-deliverysystemforcisplatinwasconstructedusingbranchedpolyethyleneimine(BPEI)asthebackbone,disulfidebondastheredox-responsivecovalentlinkerandhyaluronicacid(HA)astargetingrecognitionunitwhichcanbindselec-tivelytothereceptorofCD44,whichishighlyexpressedontheA549tumorcells.Thecisplatin-poly-ethyleneimineconjugateBPEI-SS-Ptwaspreparedandthedrugloadingofcisplatinwasupto32.66±0.06%.AfteroptimizedthecoatingweightratioofHAandBPEI-SS-Pt,thenanoparticledeliverysystemHA-(BPEI-SS-Pt)-1/4outperformedwithsmallerparticlesizeof159.0±21.0nm,narrowpolydispersityindex(PDI)of0.069±0.022andhighercisplatinloadingof29.23±0.18%,showingspecifictumor-targeting