Folate-Linked Nanoparticles Formed with DNA Complexes in Sodium Chloride Solution Enhance Transfection Efficiency
Abstract:To enhance folate-targeted transfection efficiency, we improved folate-linked cationic nanoparticles by using cholesteryl-3-carboxyamidoethylene-N-hydroxylamine (OH-Chol) as a cationic lipid and examined DNA complex (nanoplex) formation in NaCl solution. Nanoparticles (NP) were composed of OH-Chol and Tween 80, and NP-F was composed of folate–poly(ethylene glycol)–distearoylphosphatidylethanolamine conjugate (f-PEG2000-DSPE) incorporated into NP. When the NP or NP-F nanoplex was formed in NaCl solution, the transfection activity in human nasopharyngeal cancer cells (KB cells) increased along with the concentration of NaCl, and NP-F formed a larger nanoplex and showed stronger transfection activity than NP. Confocal and flow cytometric analysis demonstrated that the nanoplexes formed in 50 mM NaCl solution extensively enhanced cellular uptake. Furthermore, the NP-F nanoplex formed in 50 mM NaCl solution could dissociate DNA better than the NP nanoplex. The NP-F nanoplex formed in 50 mM NaCl solution showed 6.6- and 18.9-fold enhancement of transfection activity with specific receptor association with KB cells, relative to NP-F formed in water at a charge ratio (+/−) of 1/1 and 3/1, respectively. The results of the experiments have provided optimal conditions to form folate-linked nanoparticle complexes with DNA for folate-targeted gene delivery.
Document Type: Research Article
Publication date: 2005-06-01
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