Electroporation-Induced Electrosensitization 英文参考文献.docVIP

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Electroporation-Induced Electrosensitization 英文参考文献.doc

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Electroporation-Induced Electrosensitization 英文参考文献

Electroporation-InducedElectrosensitization OlgaN.Pakhomova1,BetsyW.Gregory1,VeraA.Khorokhorina1,AngelaM.Bowman1,ShuXiao1,2, AndreiG.Pakhomov1* 1FrankReidyResearchCenterforBioelectrics,OldDominionUniversity,Norfolk,Virginia,UnitedStatesofAmerica,2DepartmentofElectricalandComputerEngineering, OldDominionUniversity,Norfolk,Virginia,UnitedStatesofAmerica Abstract Background: Electroporation is a method of disrupting the integrity of cell membrane by electric pulses (EPs). Electrical modeling is widely employed to explain and study electroporation, but even most advanced models show limited predictivepower.Nostudieshaveaccountedforthebiologicalconsequencesofelectroporationasafactorthataltersthe cell’ssusceptibilitytoforthcomingEPs. Methodology/PrincipalFindings:WefocusedfirstontheroleofEPrateformembranepermeabilizationandlethaleffects inmammaliancells.Theratewasvariedfrom0.001to2,000Hzwhilekeepingotherparametersconstant(2to3,750pulses of60-nsto9-msduration,1.8to13.3kV/cm).TheefficiencyofallEPtreatmentswasminimalathighratesandstartedto increasegraduallywhentheratedecreasedbelowacertainvalue.Althoughthisvaluerangedwidely(0.1–500Hz),italways corresponded to the overall treatment duration near 10s. We further found that longer exposures were more efficient irrespectiveoftheEPrate,andthatsplittingahigh-rateEPtrainintwofractionswith1–5mindelayenhancedtheeffects severalfold. Conclusions/Significance: For varied experimental conditions, EPs triggered a delayed and gradual sensitization to EPs. Whenaportionofamulti-pulseexposurewasdeliveredtoalreadysensitizedcells,theoveralleffectmarkedlyincreased. Because of the sensitization, the lethality in EP-treated cells could be increased from 0 to 90% simply by increasing the exposure duration, or the exposure dose could be reduced twofold without reducing the effect. Many applications of electroporationcanbenefitfromaccountingforsensitization,byorganizingtheexposureeithertomaximizesensitization (e.g., for sterilization) or, for other