Reduction-Triggered Self-Cross-Linked Hyperbranched Polyglycerol Nanogels for Intracellular Delivery of Drugs and Proteins

Owing to the unique advantages of combining the characteristics of hydrogels and nanoparticles, nanogels are actively investigated as a promising platform for advanced biomedical applications. In this work, a self-cross-linked hyperbranched polyglycerol nanogel is synthesized using the thiol–disulfide exchange reaction based on a novel disulfide-containing polymer. A series of structural analyses confirm the tunable size and cross-linking density depending on the type of polymer (homo- or copolymer) and the amount of reducing agent, dithiothreitol, used in the preparation of the nanogels. The nanogels retain not only small molecular therapeutics irrespective of hydrophilic and hydrophobic nature but also large enzymes such as β-galactosidase by exploiting the self-cross-linking chemistry. Their superior biocompatibility together with the controllable release of active therapeutic agents suggests the applicability of nanogels in smart drug delivery systems.