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

Abstract

The clinical utility of emulsions as delivery vehicles is hindered by a dependence on passive release. Stimuliresponsive 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 redoxresponsive 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 nonviral gene delivery and represents a general approach to nanoemulsions that respond to endogenous stimuli.

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

“…This Account summarizes efforts in our lab over the past decade to develop nextgeneration FC NE cell detection probes. Next-generation FCbased cell detection probes will have improved sensitivity and specificity and be activatable 45 and vector-capable, 46 while retaining a focus on scalability and near-term translatability 47 . Resulting probes will be effective for interrogating aspects of the initial biodistribution of cell therapy and inflammation detection.…”

Designing Synthetic Polymers for Nucleic Acid Complexation and Delivery: From Polyplexes to Micelleplexes to Triggered Degradation

“…In one example, surfactantstabilized perfluorooctyl bromide (PFOB) nanoemulsions were used to encapsulate DNA complexed with fluorinated amines with subsequent reductive destabilization of the emulsion facilitating successful transfection. 61 In another case, N-carboxyanhydride polymerization was initiated with a fluorinated amine to yield poly(aspartamide) with pendent amines for complexation and a fluorocarbon chain end (Figure 8d). Use of the resultant C 9 F 17 −PAsp(DET) to complex DNA and encapsulate perfluoropentane and fluorinated gold nanorods produced a nanodroplet gene delivery system with enhanced contrast imaging in response to ultrasound and NIR.…”

“…Importantly, the inclusion of fluorine imparts additional function to gene delivery systems, including emulsion stabilization and imaging ability. In one example, surfactant-stabilized perfluorooctyl bromide (PFOB) nanoemulsions were used to encapsulate DNA complexed with fluorinated amines with subsequent reductive destabilization of the emulsion facilitating successful transfection . In another case, N -carboxyanhydride polymerization was initiated with a fluorinated amine to yield poly­(aspartamide) with pendent amines for complexation and a fluorocarbon chain end (Figure d).…”

Non-Ionic Fluorosurfactants for Droplet-Based in vivo Applications

“…6 We aimed to retain the biocompatibility of fluorosurfactants established for water-in-perfluorocarbon microfluidics, 20,21 yet optimize them for stabilizing perfluorocarbon-in-water droplets, which are more relevant to in vivo applications. Perfluorocarbonin-water droplets have seen utility as blood substitutes, 22 biomolecule delivery vehicles, [23][24][25] multifunctional materials for photodynamic therapy, 26 and ultrasound contrast agents, [27][28][29][30] among others. Moreover, cell-sized perfluorocarbon-in-water droplets are essential for in vivo measurements of intercellular forces, 31,32 tissue material properties, 33,34 and osmotic pressures.…”