title: Self-assembly of ternary insulin-polyethylenimine (PEI)-DNA nanoparticles for enhanced gene delivery and expression in alveolar epithelial cells.
abstract: Enhancing gene delivery and expression in alveolar epithelial cells could offer the opportunity for the treatment of acquired and inherited lung diseases. Here, we show that particle adsorption of human insulin (INS) is capable of increasing plasmid DNA (pDNA) delivery from polyethylenimine (PEI) nanoparticles specifically in alveolar epithelial cells. INS receptors were predominantly detected on alveolar but not on bronchial epithelial cells. INS was adsorbed on the surface of PEI gene vectors by spontaneous self-assembly resulting in ternary PEI-pDNA-INS nanoparticles. Surface adsorption was confirmed by particle size, surface charge, and fluorescence resonance energy transfer (FRET) measurements. INS adsorption significantly increased gene expression of PEI-pDNA nanoparticles up to 16-fold on alveolar epithelial cells but not on bronchial epithelial cells. This increased gene expression was INS receptor specific. Our results demonstrate that targeting INS receptor for gene delivery in alveolar epithelial cells represents a promising approach for enhanced gene delivery and expression.
authors.affiliation: Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Elfinger
authors.forename: Corinna
authors.initials: C
authors.lastname: Pfeifer
authors.forename: Senta
authors.initials: S
authors.lastname: Uezguen
authors.forename: Monika M
authors.initials: MM
authors.lastname: Golas
authors.forename: Bjoern
authors.initials: B
authors.lastname: Sander
authors.forename: Christof
authors.initials: C
authors.lastname: Maucksch
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aneja
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudolph
mesh_terms: D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D004847:Epithelial Cells / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D008854:Microscopy, Electron; D053758:Nanoparticles; D011094:Polyethyleneimine / Q000737:chemistry*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D014162:Transfection
chemical_list: D007328:Insulin; D011094:Polyethyleneimine; D004247:DNA