TY  - JOUR
A1  - Czysch, Christian
A1  - Medina‐Montano, Carolina
A1  - Zhong, Zifu
A1  - Fuchs, Alexander
A1  - Stickdorn, Judith
A1  - Winterwerber, Pia
A1  - Schmitt, Sascha
A1  - Deswarte, Kim
A1  - Raabe, Marco
A1  - Scherger, Maximilian
A1  - Combes, Francis
A1  - De Vrieze, Jana
A1  - Kasmi, Sabah
A1  - Sandners, Niek N.
A1  - Lienenklaus, Stefan
A1  - Koynov, Kaloian
A1  - Räder, Hans‐Joachim
A1  - Lambrecht, Bart N.
A1  - David, Sunil A.
A1  - Bros, Matthias
A1  - Schild, Hansjörg
A1  - Grabbe, Stephan
A1  - De Geest, Bruno G.
A1  - Nuhn, Lutz
T1  - Transient Lymph Node Immune Activation by Hydrolysable Polycarbonate Nanogels
JF  - Advanced Functional Materials
N2  - 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.
KW  - biodegradable
KW  - immunodrug delivery
KW  - lymph nodes
KW  - nanogels
KW  - polycarbonates
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287255
VL  - 32
IS  - 35
ER  -