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.

Nanoparticles Complexed with Gene Vectors to Promote Proliferation of Human Vascular Endothelial Cells

“…[48][49][50][51][52] Our strategy consists of the synthesis of biodegradable block copolymers based on PEI (1 800 g mol −1 ) and poly[(L-lactide)-co -(3( S )-methyl-2,5-morpholinedione)] (P(LA-co -MMD)) blocks, and the formation of nanoparticles thereof by self-assembly. [53][54][55] In our previous study, we have prepared microparticles from mPEG-b-P(MMD-co-GA)-g-PEI. The hydrodynamic diameter ranged from 144 to 205 nm because of the long PEG block (M w = 5000 g mol −1 ) formed a thick hydrophilic shell surrounding the core of the microparticle.…”

PEGylated Polyethylenimine-Entrapped Gold Nanoparticles Loaded With Gadolinium For Dual-Mode Ct/Mr Imaging Applications

“…Hyperbranched polyethylenimine (PEI) with abundant surface amines has been selected as a unqiue nanocarrier to load NPs and drugs [38][39][40][41][42][43], and the PEI surface amines could be easily functionalized [44,45]. Our previous work has shown that branched PEI can be used to either as a stabilizer to form PEI-stabilized Au NPs [46,47] or as a template to entrap Au NPs after the PEI surface amines are partially PEGylated for CT imaging of blood pool and major organs of mice [48,49].…”

Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier

“…Inhalation of the corresponding nanosized polyplexes containing the β2-AR ligand as targeting moiety showed enhanced efficacy in targeted enhanced green fluorescent protein (EGFP) gene silencing in mice [50]. Another targeting strategy for alveolar epithelial cells was implemented by spontaneously selfassembled ternary PEI-pDNA-insulin nanoparticles resulting from adsorbing insulin on the surface of gene vectors [51]. PEI-pDNA-insulin nanoparticles increased transgene expression up to 16-fold on alveolar epithelial cells but not on bronchial epithelial cell compared to plain PEI-pDNA.…”