Reduction-controlled hierarchical unpacking is proposed for the development of virus-mimicking gene carriers. Disulfide-bond-modified hyaluronic acid (HA) is deposited onto the surface of diselenide-conjugated oligoethylenimine/DNA polyplexes to form DNA/OEI-SeSex/HA-SS-COOH (DOS) polyplexes. The cleavage of the disulfide and diselenide bonds is triggered by the gradient GSH level at the tumor site and inside the cells. The transfection efficiency of DOS show significant enhancement over DNA/poly(ethylene imine) (DP) in vitro and in vivo.
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