博士申请用研究计划英文写作模板.doc

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1、pH-ResponsiveBiodegradablePolymersforIntracellularDrugDeliveryA.ProposedareaofresearchTheaimofthisproposedPhDprojectistodevelopandevaluatepHresponsive,endosomolyticpolymersforefficientintracellulardeliveryofbiologicaldrugpayloads.Thereisaneedtobetterunderstandthemechanismsofentryintothecel

2、lcytoplasmandnucleusinordertodesignoptimaldeliverysystemsforbiologicalmolecules.Ontheonehand,thiswouldopenupsignificantopportunitiestodeliverpotentdrugpayloadsagainstintracellulartargetstopositivelyimpacthumanhealth.Inadditiontheprojectaimstodevelopamoregeneralunderstandingoftherulesgovern

3、ingtheuptakeofbiologicalmoleculesintocells.Thisprojectproposestoinvestigatetheuseofsynthetic,biodegradablepolymersforintracellulardeliveryofdrugpayloads(includingsiRNA,therapeuticpeptideandantibody)againstawell-validatedintracellulardrugtarget,suchasBcl-2.ThenovelpH-responsivepolymershaveb

4、eendesignedbyDrRongjunChen’sLabtomimictheactivityofviruses,bothintheircellentryandendosomalescapemechanisms.Usingcancercelllines(JurkatorHL-60cells)asamodelsystem,thepolymerswouldbetestedwithavarietyofdifferentbiologicalpayloadsinaquantitativecomparisonoftheirabilitytoenterthecellandtrigge

5、rapoptosisandsubsequentlycelldeath.Withanefficientmodelsystemestablished,therewouldthenbescopetooptimizethesystemintermsofthekineticsandmechanismsofcellentry,cytoplasmicandnuclearlocalization,andthebiodegradationofthepolymers.Therewouldalsobescopetoexploretheefficiencyinothercellsystemsand

6、withfurtherintracellulartargets.ThismultidisciplinaryprojectisattheinterfaceofChemistry,BiologyandMedicine,andwillprovidethestudentwitharealopportunitytobeinvolvedinthedevelopmentandevaluationofnewnanomedicines.B.BackgroundAdvancesingenomicsandproteomicshaveenabledthedevelopmentofmacrodrug

7、s,suchasnucleicacidsandproteins,withpotentialforthetreatmentofawidevarietyofdiseases.Amongstotherproblems,theirclinicalapplicationsmaybegreatlyimpairedbylowcellularuptakeandlysosomaldegradationbeforetheycanreachtheirtargetorganellesorcellnuclei.Inordertoachiev