Electroporation-based delivery of cell-penetrating peptide conjugates of peptide nucleic acids for antisense inhibition of intracellular bacteria

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dc.contributorVirginia Tech. School of Biomedical Engineering and Sciencesen
dc.contributorVirginia Tech. Department of Biomedical Sciences and Pathobiologyen
dc.contributorVirginia Tech. Department of Chemical Engineeringen
dc.contributor.authorMa, Saien
dc.contributor.authorSchroeder, Betsyen
dc.contributor.authorSun, Chenen
dc.contributor.authorLoufakis, Despina N.en
dc.contributor.authorCao, Zhenningen
dc.contributor.authorSriranganathan, Nammalwaren
dc.contributor.authorLu, Changen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessed2015-04-15en
dc.date.accessioned2015-04-20T22:22:11Zen
dc.date.available2015-04-20T22:22:11Zen
dc.date.issued2014-08-14en
dc.description.abstractCell penetrating peptides (CPPs) have been used for a myriad of cellular delivery applications and were recently explored for delivery of antisense agents such as peptide nucleic acids (PNAs) for bacterial inhibition. Although these molecular systems (i.e. CPP–PNAs) have shown ability to inhibit growth of bacterial cultures in vitro, they show limited effectiveness in killing encapsulated intracellular bacteria in mammalian cells such as macrophages, presumably due to difficulty involved in the endosomal escape of the reagents. In this report, we show that electroporation delivery dramatically increases the bioavailability of CPP–PNAs to kill Salmonella enterica serovar Typhimurium LT2 inside macrophages. Electroporation delivers the molecules without involving endocytosis and greatly increases the antisense effect. The decrease in the average number of Salmonella per macrophage under a 1200 V cm_1 and 5 ms pulse was a factor of 9 higher than that without electroporation (in an experiment with a multiplicity of infection of 2 : 1). Our results suggest that electroporation is an effective approach for a wide range of applications involving CPP-based delivery. The microfluidic format will allow convenient functional screening and testing of PNA-based reagents for antisense applications.en
dc.description.notesSupplementary information is included in a separate fileen
dc.description.sponsorshipVirginia Tech. Institute for Critical Technology and Applied Science. NanoBio Thrusten
dc.description.sponsorshipNational Science Foundation (U.S.) - CBET grant 1016547en
dc.description.sponsorshipNational Science Foundation (U.S.) - CBET grant 0967069en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMa, S., Schroeder, B., Sun, C., Loufakis, D. N., Cao, Z., Sriranganathan, N., & Lu, C. (2014). Electroporation-based delivery of cell-penetrating peptide conjugates of peptide nucleic acids for antisense inhibition of intracellular bacteria. Integrative Biology, 6(10), 973-978. doi: 10.1039/C4IB00172Aen
dc.identifier.doihttps://doi.org/10.1039/C4IB00172Aen
dc.identifier.issn1757-9694en
dc.identifier.urihttp://hdl.handle.net/10919/51725en
dc.identifier.urlhttp://pubs.rsc.org/en/content/articlelanding/2014/ib/c4ib00172aen
dc.language.isoenen
dc.publisherThe Royal Society of Chemistryen
dc.relation.ispartofseriesOpen access articles from Integrative Biologyen
dc.relation.urihttp://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=ib&themeid=ab0f94be-eff2-4286-b96e-367458372850en
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.subjectCell penetrating peptidesen
dc.subjectPeptide nucleic acidsen
dc.subjectElectroporationen
dc.subjectBacterial inhibitionen
dc.titleElectroporation-based delivery of cell-penetrating peptide conjugates of peptide nucleic acids for antisense inhibition of intracellular bacteriaen
dc.title.serialIntegrative Biologyen
dc.typeArticle - Refereeden
dc.typeDataseten
dc.type.dcmitypeTexten
dc.type.dcmitypeDataseten

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