Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators
Anne Huppertsberg, Leonard Kaps, Zifu Zhong, Sascha Schmitt, Judith Stickdorn, Kim Deswarte, Francis Combes, Christian Czysch, Jana De Vrieze, Sabah Kasmi, Niklas Choteschovsky, Adrian Klefenz, Carolina Medina‐Montano, Pia Winterwerber, Chaojian Chen, Matthias Bros, Stefan Lienenklaus, Niek N. Sanders, Kaloian Koynov, Detlef Schuppan, Bart N. Lambrecht, Sunil A. David, Bruno G. De Geest, Lutz Nuhn
Abstract
, however, we observed a remarkable impact of the nanogel: After intravenous injection, a spatially controlled immunostimulatory activity was evident in the spleen, whereas systemic off-target inflammatory responses triggered by the small-molecular imidazoquinoline analogue were absent. These findings underline the potential of squaric ester-based, pH-degradable nanogels as a promising platform to permit intravenous administration routes of small-molecular TLR7/8 agonists and, thus, the opportunity to explore their adjuvant potency for systemic vaccination or cancer immunotherapy purposes.