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CellularUptake of siRNA NanoparticlesforDrugDeliveryinWhole BloodandLymphocytes
The newestfrontierof drugdeliveryanddisease treatmentisnanotechnologyutilizingtherapeutic
nucleicacids,whichare provingtobe fullycustomizable,programmable andcancarry multiple
functionalities.Nucleicacidbasednanoparticlesfunctionalizedwithmultiple shortinterference RNAs
(siRNAs),orothertherapeuticoligonucleotidesandformulatedwithlipid-like carriersforefficient
intracellulardeliverycanactas an active pharmaceutical ingredient.Due tothe route of administration,
it isimportantto studyhowthisnewtherapeutictechnologyinteractswithbloodandlymphocytesto
elucidate possibleundesirable side-effects.
Thisinvestigationexaminesthe cellularuptake bywholebloodandbylymphocyte isolationsfrom
humandonorsof several fluorescentlytaggedfunctional RNA nanoparticlesselectedfromthe
laboratorylibrary.Lymphocytesare isolatedfromeachwhole bloodsample andthe siRNA nanoparticles
formulatedwithpolycationiccarriersare introducedtoboththe whole bloodand lymphocyte isolation.
Fluorescence changesindicatingthe relative uptake of nano-formulationsbybloodcellsare measured
viaflowcytometryandfurtheranalyzed.Experimentationhasthusfarshowna markeddifferencein
nanoparticle uptake whenthe formulationisintroducedafterthe samplesare seriallydilutedas
opposedtointroductiontoundilutedhumanbloodsamples.Thismayindicate thatthe currentlyused
experimental protocolmayaffectapoptosisandcell morphologyof lymphocytesthuspromoting their
interactionwithnanoparticles.Furtherexperimentationaimstoexaminewhichconstructsandcells
have the most efficientcellularuptake bybloodcells,whichlipid-like carrierworksbestforuptake and
mechanismsforcellularentry.

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siRNA Nanoparticle Uptake in Blood and Lymphocytes

  • 1. CellularUptake of siRNA NanoparticlesforDrugDeliveryinWhole BloodandLymphocytes The newestfrontierof drugdeliveryanddisease treatmentisnanotechnologyutilizingtherapeutic nucleicacids,whichare provingtobe fullycustomizable,programmable andcancarry multiple functionalities.Nucleicacidbasednanoparticlesfunctionalizedwithmultiple shortinterference RNAs (siRNAs),orothertherapeuticoligonucleotidesandformulatedwithlipid-like carriersforefficient intracellulardeliverycanactas an active pharmaceutical ingredient.Due tothe route of administration, it isimportantto studyhowthisnewtherapeutictechnologyinteractswithbloodandlymphocytesto elucidate possibleundesirable side-effects. Thisinvestigationexaminesthe cellularuptake bywholebloodandbylymphocyte isolationsfrom humandonorsof several fluorescentlytaggedfunctional RNA nanoparticlesselectedfromthe laboratorylibrary.Lymphocytesare isolatedfromeachwhole bloodsample andthe siRNA nanoparticles formulatedwithpolycationiccarriersare introducedtoboththe whole bloodand lymphocyte isolation. Fluorescence changesindicatingthe relative uptake of nano-formulationsbybloodcellsare measured viaflowcytometryandfurtheranalyzed.Experimentationhasthusfarshowna markeddifferencein nanoparticle uptake whenthe formulationisintroducedafterthe samplesare seriallydilutedas opposedtointroductiontoundilutedhumanbloodsamples.Thismayindicate thatthe currentlyused experimental protocolmayaffectapoptosisandcell morphologyof lymphocytesthuspromoting their interactionwithnanoparticles.Furtherexperimentationaimstoexaminewhichconstructsandcells have the most efficientcellularuptake bybloodcells,whichlipid-like carrierworksbestforuptake and mechanismsforcellularentry.