Nanoparticles Functionalized with Polymer Brushes for Gene Delivery

Although the field of gene delivery has made tremendous progress, many obstacles remain to achieve safe, targeted, and controlled delivery and release of nucleic acids. The effective delivery of these therapeutics requires the precise control of physicochemical and biochemical processes regulating a broad range of events, from initial complexation and stabilization in biological fluids, to the crossing of endothelial barriers, internalization, and cytosolic/nuclear release. Polymer brush‐functionalized nanoparticles are well suited to control physicochemical parameters that regulate these processes, including the chemical composition of their shell; its grafting density and thickness; as well as the size, shape, and physical properties of its core. In addition, polymer brushes can be designed to display more complex architectures (blocks and mixed brushes), providing further control of the delivery vehicle physicochemistry, size, and hierarchical structure. Here, this study discusses how gene delivery systems can be uniquely engineered, tailoring the physicochemistry of polymer brush‐functionalized nanoparticles. In addition, it reviews the impact of brush design on the formation of protein coronas, associated with in vitro transfection, blood circulation, or cytosolic entry. Finally, it discusses how polymer brush engineering enables the design of nanomaterials for theranostics applications.