A series of water-soluble telechelic dithiol monomers bearing multiple guanidinium ion (Gu(+)) tints in their main chains were synthesized for packaging siRNA by template-assisted oxidative polymerization at their thiol termini. In the presence of siRNA, oxidative polymerization of (TEG)Gu(4) affords a uniform-sized (7 +/- 2 nm) nanocaplet containing siRNA (P(TEG)Gu(4)superset of siRNA; p(TEG)Gu(4) = polymerized (TEG)Gu(4)) When this small conjugate is incubated with live cells, cellular uptake occurs, and the nanocaplet undergoes depolymerization in the reductive cytosolic environment to liberate the packaged siRNA. Consequently, gene expression in the live cells is suppressed.