Synthesis and Characterization of Free Radical Scavenging Dendrimer Nanogels via Cross-Linking Reaction-Enabled Flash Nanoprecipitation

This work reports the development and evaluation of dendrimer-based nanogels based on polyamidoamine (PAMAM) dendrimer generation 5, engineered to act as a carrier with reactive oxygen species (ROS)-scavenging capabilities. We developed a cross-linking reaction-enabled flash nanoprecipitation method in which the cross-linking reaction occurs during the flash nanoprecipitation process to form a cross-linked nanostructure. Using this approach, an <i>N</i>-hydroxysuccinimide (NHS)-functionalized ROS-responsive thioketal cross-linker (TK-NHS) was synthesized and utilized to cross-link DAB-core PAMAM dendrimer G5, resulting in the formation of G5-TK nanogels. The resulting nanogels were characterized using dynamic light scattering and transmission electron microscopy, and their cytocompatibility, irritancy, cellular uptake, and ROS scavenging activity were assessed. We confirmed the ROS scavenging capability of these nanogels and observed favorable safety profiles. The G5-TK nanogels can be further developed as carriers for therapeutic delivery applications to treat oxidative stress-related pathological conditions.