@article{CzyschMedina‐MontanoZhongetal.2022, author = {Czysch, Christian and Medina-Montano, Carolina and Zhong, Zifu and Fuchs, Alexander and Stickdorn, Judith and Winterwerber, Pia and Schmitt, Sascha and Deswarte, Kim and Raabe, Marco and Scherger, Maximilian and Combes, Francis and De Vrieze, Jana and Kasmi, Sabah and Sandners, Niek N. and Lienenklaus, Stefan and Koynov, Kaloian and R{\"a}der, Hans-Joachim and Lambrecht, Bart N. and David, Sunil A. and Bros, Matthias and Schild, Hansj{\"o}rg and Grabbe, Stephan and De Geest, Bruno G. and Nuhn, Lutz}, title = {Transient Lymph Node Immune Activation by Hydrolysable Polycarbonate Nanogels}, series = {Advanced Functional Materials}, volume = {32}, journal = {Advanced Functional Materials}, number = {35}, doi = {10.1002/adfm.202203490}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287255}, year = {2022}, abstract = {The development of controlled biodegradable materials is of fundamental importance in immunodrug delivery to spatiotemporally controlled immune stimulation but avoid systemic inflammatory side effects. Based on this, polycarbonate nanogels are developed as degradable micellar carriers for transient immunoactivation of lymph nodes. An imidazoquinoline-type TLR7/8 agonist is covalently conjugated via reactive ester chemistry to these nanocarriers. The nanogels not only provide access to complete disintegration by the hydrolysable polymer backbone, but also demonstrate a gradual disintegration within several days at physiological conditions (PBS, pH 6.4-7.4, 37 °C). These intrinsic properties limit the lifetime of the carriers but their payload can still be successfully leveraged for immunological studies in vitro on primary immune cells as well as in vivo. For the latter, a spatiotemporal control of immune cell activation in the draining lymph node is found after subcutaneous injection. Overall, these features render polycarbonate nanogels a promising delivery system for transient activation of the immune system in lymph nodes and may consequently become very attractive for further development toward vaccination or cancer immunotherapy. Due to the intrinsic biodegradability combined with the high chemical control during the manufacturing process, these polycarbonate-based nanogels may also be of great importance for clinical translation.}, language = {en} }