Encapsulation of negatively charged plasmid DNA into a small-sized nanocapsule without using any condensing agent is very challenging up to now. Here we report a versatile method for encapsulating large-sized plasmid DNAs into small-sized bioreducible nanocapsules in which shearing force and surfactant can fold large-sized plasmid DNAs into small-sized emulsion droplets containing bioreducible branched polymers. Subsequently, temperature triggers the bioreducible branched polymers to aggregate and cross-link at the water/oil interface of the emulsion nanodroplet, forming a bioreducible shell around the nanodroplet. Thus, a small-sized nanocapsule (∼110 nm) containing large-sized plasmid DNA (∼1900 nm long) forms by removal of the surfactant.
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