Water-soluble polycationic dendrimers with a phosphoramidothioate backbone: preliminary studies of cytotoxicity and oligonucleotide/plasmid delivery in human cell culture.
A series of water-soluble polycationic dendrimers with a phosphoramidothioate backbone (P-dendrimers) was studied in human cell culture. Preliminary studies have shown that P-dendrimers of series 1 and 2, possessing N,N-diethyl-ethylenediamine hydrochloride functions at the surface, show rather moderate cytotoxicity toward HeLa, HEK 293, and HUVEC cells in a standard MTT assay in serum-containing medium, generally lower than lipofectin. The experiments of cellular uptake have shown the necessity for the presence of serum for transfection with P-dendrimers of series 1 and 2. These compounds efficiently delivered fluorescein-labeled oligodeoxyribonucleotide into HeLa cells in serum-containing medium, but they failed to do so in HUVEC cell culture. The dendrimers were found to be successful mediators of transfection of the HeLa cells with a DNA plasmid containing the functional gene of enhanced green fluorescent protein (EGFP).
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 90-363 Lodz, Poland.
Maria
M
Maszewska
Julien
J
Leclaire
Marcin
M
Cieslak
Barbara
B
Nawrot
Andrzej
A
Okruszek
Anne-Marie
AM
Caminade
Jean-Pierre
JP
Majoral
D002470:Cell Survival; D042783:Endothelial Cells; D019793:Fluorescein; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010710:Phosphates / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000633:toxicity; D010957:Plasmids
D009841:Oligonucleotides; D010710:Phosphates; D010714:Phosphatidylethanolamines; C058091:phosphoramidothioic acid; C020888:1,2-dielaidoylphosphatidylethanolamine; D019793:Fluorescein