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寡聚荷正电氨基酸修饰的基因递送纳米脂质载体的构建和初步评价.docx

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寡聚荷正电氨基酸修饰的基因递送纳米脂质载体的构建和初步评价 Title:ConstructionandPreliminaryEvaluationofGeneDeliveryNanolipidCarrierModifiedwithCationicAminoAcidforOligomerization Abstract: Genedeliverysystemsplayacrucialroleinfacilitatingthedeliveryoftherapeuticgenesintotargetcellsforthetreatmentofvariousdiseases.Inthisstudy,weaimedtoconstructandevaluateagenedeliverynanolipidcarriermodifiedwithcationicaminoacidforoligomerization.Thecarrierwasdesignedtoenhancegenedeliveryefficiencyandstability,ultimatelyimprovingtherapeuticoutcomes. Introduction: Genetherapyholdsgreatpromiseforthetreatmentofgeneticandacquireddiseases.However,thesuccessofgenetherapyheavilyreliesonthedevelopmentofefficientandsafegenedeliverysystems.Lipid-basednanocarriershavereceivedconsiderableinterestduetotheirabilitytoencapsulateandprotectgenes,aswellastheirversatilityinsurfacemodification.Themodificationofnanocarrierswithcationicaminoacidsoffersapromisingstrategyforimprovinggenedeliveryefficiencythroughenhancedcellularuptake. Methods: 1.LipidNanoparticle(LNP)Synthesis:LNPweresynthesizedusingathin-filmhydrationmethod,followedbyextrusiontoobtainuniformsizeandshape. 2.ModificationwithCationicAminoAcids:Cationicaminoacids,suchaslysineandarginine,wereconjugatedtothesurfaceofLNPthroughsuitablelinkers.Theconjugationefficiencyandstabilitywereevaluated. 3.OligomerizationCapability:TheabilityofmodifiedLNPtofacilitategeneoligomerizationwasinvestigatedusingoligonucleotideswithadesignatedsequence. 4.GeneDeliveryEfficiency:ThemodifiedLNPwereloadedwithareportergene,andtheirabilitytodelivergenesintotargetcellswasassessedbymeasuringgeneexpressionlevels. 5.CytotoxicityEvaluation:CellviabilityassayswereperformedtodeterminethebiocompatibilityofthemodifiedLNP. Results: 1.LNPModification:CationicaminoacidsweresuccessfullyconjugatedtothesurfaceofLNP,asconfirmedbyspectroscopicanalysis. 2.OligomerizationCapability:ThemodifiedLNPshowedanincreasedabilitytofacilitategeneoligomerization,asobservedthroughgelelectrophoresis. 3.GeneDeliveryEfficiency:Themodi