Silicalite nanoparticles that promote transgene expression

Abstract

Here, we report on a new zeolite-based silicalite nanoparticle that can enhance the transfection efficiencies generated by poly ethylene imine-plasmid DNA (PEI-pDNA) complexes via a sedimentation mechanism and can enhance the transfection efficiencies of pDNA alone when surface functionalized with amine groups. The silicalite nanoparticles have a mean size of 55 nm. Functionalizing the silicalite nanoparticles with amine groups results in a clear transition in zeta potential from -25.9 ± 2.3 mV (pH 7.4) for unfunctionalized silicalite nanoparticles to 4.9 ± 0.7 mV (pH 7.4) for amine functionalized silicalite nanoparticles. We identify that silicalite nanoparticles used to promote non-viral vector acceleration to the cell surface are found in acidic vesicles or the cytoplasm but not the nucleus. An MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay showed that the silicalite nanoparticles were non-toxic at the concentrations tested for transfection. We show that surface functionalization of silicalite nanoparticles with amine groups results in a significant (230%) increase in transfection efficiency of pDNA when compared to unfunctionalized silicalite nanoparticles. Silicalite nanoparticles enhanced pDNA-PEI induced transfection of human embryonic kidney (HEK-293) cells by over 150%.

Review: Bioanalytical applications of biomolecule-functionalized nanometer-sized doped silica particles

“…Zeolite-based silicalite nanoparticles generated with poly(ethylenimine)-plasmid DNA (PEI-pDNA) complexes via a sedimentation mechanism, can also promote transgene expression and improve transfection efficiencies when their surfaces are functionalized with amine groups [199]. The method used is very much akin to the generation of cationic polymers, but acts without the addition of other cationic transfection reagents.…”

Synthesis and characterization of mannosylated pegylated polyethylenimine as a carrier for siRNA

“…However, concerns about their immunogenic nature and inadvertent gene expression changes following random integration into the host genome still exist (Abbas et al, 2008; Martin and Caplen, 2007). Polyethylenimine (PEI) is a synthetic cationic polymer that has been widely used to deliver oligonucleotides, siRNA and plasmid DNA in vitro and in vivo (Abbas et al, 2008; Aigner et al, 2002; Boussif et al, 1995; Hobel and Aigner, 2010; Intra and Salem, 2008; Nimesh and Chandra, 2009; Pearce et al, 2008; Petersen et al, 2002; Zhang et al, 2008; Zintchenko et al, 2008b). PEI electrostatically condenses nucleic acids and forms stable nanoparticles or polyplexes (Intra and Salem, 2008).…”

Optimized dextran–polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments

“…Therefore, delivery vehicles such as cationic lipids or polymers are often utilized to improve the transfection efficiencies of pDNA. Cationic polymers such as polyethylenimine (PEI) can bind with pDNA electrostatically to form complexes which protect DNA from degradation in blood serum (Intra and Salem, 2008, 2011; Pearce et al, 2008). In addition, net positive surface charges achieved using appropriate nitrogen to phosphate (N/P) ratios can facilitate the uptake of complexes by cells.…”