Redox‐Responsive Gene Delivery from Perfluorocarbon Nanoemulsions through Cleavable Poly(2‐oxazoline) Surfactants

The clinical utility of emulsions as delivery vehicles is hindered by a dependence on passive release. Stimuli‐responsive emulsions overcome this limitation but rely on external triggers or are composed of nanoparticle‐stabilized droplets that preclude sizes necessary for biomedical applications. Here, we employ cleavable poly(2‐oxazoline) diblock copolymer surfactants to form perfluorocarbon (PFC) nanoemulsions that release cargo upon exposure to glutathione. These surfactants allow for the first example of redox‐responsive nanoemulsions in cellulo. A noncovalent fluorous tagging strategy is leveraged to solubilize a GFP plasmid inside the PFC nanoemulsions, whereupon protein expression is achieved selectively when employing a stimuli‐responsive surfactant. This work contributes a methodology for non‐viral gene delivery and represents a general approach to nanoemulsions that respond to endogenous stimuli. A disulfide‐linked poly(2‐oxazoline) surfactant allows for stabilization of perfluorocarbon‐in‐water nanoemulsions. Upon reduction, the surfactant is cleaved, triggering destabilization and subsequent release of the encapsulated payload. Stimuli‐responsive behavior is achieved selectively in high concentrations of reducing agent, allowing for delivery of fluorous‐tagged plasmid DNA encoding for enhanced green fluorescent protein.