A Molecular Umbrella Approach
to the Intracellular
Delivery of Small Interfering RNA
- Publication date
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Abstract
A series of diwalled and tetrawalled molecular umbrellas
have been
synthesized using cholic acid, spermidine, and lysine as starting
materials. Coupling of these molecular umbrellas to an octaarginine
peptide afforded agents that were capable of promoting the transport
of small interfering RNA to HeLa cells, as judged by the knockdown
of enhanced green fluorescent protein expression. The efficiency of
this knockdown was found to increase with an increasing number of
facially amphiphilic walls present, and also when a cleavable disulfide
linker was replaced with a noncleavable, maleimido moiety; i.e., a
group that is not susceptible to thiolate-disulfide interchange. The
knockdown efficiency that was observed for one tetrawalled molecular
umbrella–octaargine conjugate was comparable to that observed
with a commercially available transfection agent, Lipofectamine 2000,
but the conjugate showed less cytotoxicity
