Transient Lymph Node Immune Activation by Hydrolysable Polycarbonate Nanogels. (26th June 2022)

• Record Type: Journal Article
• Authors: Czysch, Christian; Medina‐Montano, Carolina; Zhong, Zifu; Fuchs, Alexander; Stickdorn, Judith; Winterwerber, Pia; Schmitt, Sascha; Deswarte, Kim; Raabe, Marco; Scherger, Maximilian; Combes, Francis; De Vrieze, Jana; Kasmi, Sabah; Sandners, Niek N.; Lienenklaus, Stefan; Koynov, Kaloian; Räder, Hans‐Joachim; Lambrecht, Bart N.; David, Sunil A.; Bros, Matthias; Schild, Hansjörg; Grabbe, Stephan; De Geest, Bruno G.; Nuhn, Lutz
• Is Part Of: Advanced functional materials. Volume 32:Number 35(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-26
• Subjects: biodegradable -- immunodrug delivery -- lymph nodes -- nanogels -- polycarbonates; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202203490
• Languages: English
• ISSNs: 1616-301X

Abstract

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. Abstract : Hydrophilic polycarbonate‐based nanogels allow for a gradual hydrolysis under physiological conditions. Via reactive ester chemistry self‐assembled polycarbonate block copolymer micelles are covalently crosslinked and equipped with TLR7/8 immunodrugs. Administering these nanogels subcutaneously enables a localized delivery to draining lymph nodes resulting in a spatio‐temporal control over the immunostimulation.