Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells.
Branched polyethylenimine (PEI) chains with an average molecular mass of 2 kDa (PEI2) have been covalently attached to gold nanoparticles (GNPs), and the potency of the resulting PEI2-GNPs conjugates as vectors for the delivery of plasmid DNA into monkey kidney (COS-7) cells in the presence of serum in vitro has been systematically investigated. The transfection efficiencies vary as a function of the PEI/gold molar ratio in the conjugates, with the best one (PEI2-GNPII) being 12 times more potent than the unmodified polycation. This potency can be further doubled by adding amphiphilic N-dodecyl-PEI2 during complex formation with DNA. The resulting ternary complexes are at least 1 order of magnitude more efficient than the 25-kDa PEI, one of the premier polycationic gene-delivery vectors. Importantly, although unmodified PEI2 transfects just 4% of the cells, PEI2-GNPII transfects 25%, and the PEI2-GNPII/dodecyl-PEI2 ternary complex transfects 50% of the cells. The intracellular trafficking of the DNA complexes of these vectors, monitored by transmission electron microscopy, has detected the complexes in the nucleus <1 h after transfection.
Thomas
Mini
M
Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Klibanov
Alexander M
AM
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002863:Chromogenic Compounds / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005697:Galactosides / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008854:Microscopy, Electron; D008956:Models, Chemical; D036103:Nanotechnology; D010957:Plasmids / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry*; D013053:Spectrophotometry; D013997:Time Factors; D014162:Transfection
D002863:Chromogenic Compounds; D005697:Galactosides; D007211:Indoles; D006046:Gold; D011094:Polyethyleneimine; D004247:DNA; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside