To fully harness the potential of advanced therapeutics, various delivery scenarios must be handled. Polymer-based, core-crosslinked, fully hydrophilic nanogels are a promising platform to tackle these drug delivery challenges. In contrast to micellar delivery systems, nanogels have a stable morphology even in vivo. And compared to lipid-based systems, they feature no innate immune activity and are chemically more easily and precisely modifiable. Over the years we have introduced a stepwise synthesis strategy starting from monomer synthesis, block copolymerization and self-assembly, followed by further functionalization as well as core-crosslinking. This robust process allows for customization of the final nanogel during every step. Nanogels can transport a wide array of drugs, ranging from covalently bound or non-covalently encapsulated small molecules to electrostatically bound nucleic acids. Additionally, targeting motives like carbohydrates, peptides or nanobodies can be attached to the surface. The current generation of nanogels is importantly biodegradable and features various modes of disassembly that respond to different environmental triggers. We foresee a promising future for this evolving platform using the toolbox that chemistry provides to foster drug co-delivery, enhance degradability and adapt to future trends such as personalized medicine and AI. Polymer-based, core-crosslinked, fully hydrophilic nanogels are a promising platform to tackle the challenge of drug delivery. The diverse chemical toolbox allows for loading with small molecule as well as nucleic acid drugs and surface modification to achieve cell targeting. The nanogels can respond to environmental triggers and feature multiple modes of degradation. • Nanogels are polymer-based, core-crosslinked, fully hydrophilic nanoparticles. • Their chemical structure allows for diverse cargo loading and surface modification. • They have multiple degradation modes and responsiveness to environmental triggers.
Fuchs et al. (Wed,) studied this question.