We report the evaluation of poly(-alkylaminosiloxane) as a novel class of polycationic DNA carriers. Controlled hydrolysis of mono- and di-aminoalkylmethyldimethoxysilane provided a wide range of defined oligomeric mixtures. Basic hydrolysis conditions yielded mixtures composed mainly of cyclic and long linear oligomers, while under acidic conditions mainly short-linear oligomers were derived. They all efficiently interacted with plasmid DNA as revealed by electron microscopy and DNA retardation assays. However, only diamine-based oligomers prepared under basic conditions were able to mediate substantial levels of DNA transfection in human HeLa cells. SiDA1b, prepared by basic hydrolysis of 3-(2-aminoethylamino)propyl-methyl-dimethoxysilane, was found to be at least as efficient as the frequently used cationic transfection agents DOTAP and polyethylenimine (PEI). The transfection activity was sensitive to bafilomycin A1, suggesting a mechanism that depends on proton capture during the acidification process associated with endocytosis.
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