Facile synthesis of size‐tunable multihydroxy nanogels by self‐assembly‐induced disulfide bonds crosslinking

Abstract Significant advancements have been achieved in polymer nanogel synthesis, yet there is a dearth of methods for easily preparing size‐adjustable, surface‐modifiable, and biocompatible nanogels. This study introduces a straightforward method for fabricating hyperbranched polyglycerol (HPG) nanogels in water through self‐assembly and disulfide bond crosslinking, avoiding the use of surfactants. The process involves modifying HPG with thioctic acid (TA) to create amphiphilic HPG‐TA rich in disulfide bonds, which is then reduced to facilitate water introduction and self‐assembly. Photocrosslinking is used to finalize the formation of HPG nanogels. These nanogels feature a uniform size distribution, with hydrodynamic diameters tunable from around 90 to 400 nm by tweaking synthesis variables. They have shown low cytotoxicity and high stability in aqueous media, with notable sensitivity to pH, especially in acidic conditions (e.g., pH 3), and redox‐responsiveness, as evidenced by reactions to 10 mM dithiothreitol (DTT). The nanogels' multiple hydroxyl groups enable easy functionalization, exemplified by the synthesis of fluorescent HPG‐RB nanogels. This work presents an efficient strategy for producing robust HPG nanogels, potentially spurring further advancements in the field of polymer nanogel synthesis and application.