Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators
In this paper Nuhn et al. report on a novel nanocarrier platform based on polymerizable squaric ester amides for a hydrolysis-resistant post-polymerization modification of pH-degradable, immunodrug-loaded nanogels. In vivo investigations of the nanocarrier demonstrated after intravenous administration a spatially controlled immunostimulatory activity in the spleen, whereas, in contrast to the free immunodrug, systemic off-target inflammatory responses were absent. These findings underline the nanocarrier's potential to permit safe intravenous administration of immune modulators and explore their potency in systemic vaccination or cancer imunotherapy.