Thermoresponsive cationic dendronized copolymers and their corresponding nanogels as smart gene carriers

Dendronization of polymers enhances the crowding and cooperative effects to provide efficient encapsulation and protection of biomacromolecules, which may provide a new strategy for developing novel advanced biomaterials. In the present work, a class of thermoresponsive dendronized copolymers and their corresponding nanogels were prepared, and their properties as siRNA carriers were investigated. These copolymer materials are constituted with ethoxyl- and amino-terminated dendritic oligoethylene glycol (OEG) moieties to provide thermoresponsiveness and positive charges for specific interaction with siRNA, respectively. Multivalency from the dendritic architecture affords these cationic copolymer materials appropriate compositions for efficient condensation with negatively charged siRNAs, and provides excellent protection for them. Thermoresponsive properties from the OEG dendrons can favorably trigger the release of encapsulated siRNAs through the collapse of copolymer chains upon phase transitions at physiological temperature. In comparison with the copolymers, the corresponding nanogels show favorable propensity to condensate, protect, and efficiently release siRNAs even when a low amount of ammonium units was presented. The enhanced proximity effects from intermolecularly appended dendrons within the spherical morphology of nanogels are remarkable. The nanogels/siRNA complex can be taken up efficiently by the cells, and greatly knock down the expression of target genes. These features guarantee dendronized copolymer-based nanogels as highly promising vectors for gene delivery.