pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Nuhn, LutzVanparijs, Nane
De Beuckelaer, Ans
Lybaert, Lien
Verstraete, Glenn
Deswarte, Kim
Lienenklaus, Stefan
Shukla, Nikunj M
Salyer, Alex C D
Lambrecht, Bart N
Grooten, Johan
David, Sunil A
De Koker, Stefaan
De Geest, Bruno G
Issue Date
2016-07-19
Metadata
Show full item recordAbstract
Agonists of Toll-like receptors (TLRs) are potent activators of the innate immune system and hold promise as vaccine adjuvant and for anticancer immunotherapy. Unfortunately, in soluble form they readily enter systemic circulation and cause systemic inflammatory toxicity. Here we demonstrate that by covalent ligation of a small-molecule imidazoquinoline-based TLR7/8 agonist to 50-nm-sized degradable polymeric nanogels the potency of the agonist to activate TLR7/8 in in vitro cultured dendritic cells is largely retained. Importantly, imidazoquinoline-ligated nanogels focused the in vivo immune activation on the draining lymph nodes while dramatically reducing systemic inflammation. Mechanistic studies revealed a prevalent passive diffusion of the nanogels to the draining lymph node. Moreover, immunization studies in mice have shown that relative to soluble TLR7/8 agonist, imidazoquinoline-ligated nanogels induce superior antibody and T-cell responses against a tuberculosis antigen. This approach opens possibilities to enhance the therapeutic benefit of small-molecule TLR agonist for a variety of applications.Citation
pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation. 2016, 113 (29):8098-103 Proc. Natl. Acad. Sci. U.S.A.Affiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.PubMed ID
27382168Type
ArticleLanguage
enISSN
1091-6490ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1600816113
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
Related articles
- Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist.
- Authors: Nuhn L, Van Hoecke L, Deswarte K, Schepens B, Li Y, Lambrecht BN, De Koker S, David SA, Saelens X, De Geest BG
- Issue date: 2018 Sep
- Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses.
- Authors: Dowling DJ, Scott EA, Scheid A, Bergelson I, Joshi S, Pietrasanta C, Brightman S, Sanchez-Schmitz G, Van Haren SD, Ninković J, Kats D, Guiducci C, de Titta A, Bonner DK, Hirosue S, Swartz MA, Hubbell JA, Levy O
- Issue date: 2017 Nov
- Control over Imidazoquinoline Immune Stimulation by pH-Degradable Poly(norbornene) Nanogels.
- Authors: Kockelmann J, Stickdorn J, Kasmi S, De Vrieze J, Pieszka M, Ng DYW, David SA, De Geest BG, Nuhn L
- Issue date: 2020 Jun 8
- Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators.
- Authors: Huppertsberg A, Kaps L, Zhong Z, Schmitt S, Stickdorn J, Deswarte K, Combes F, Czysch C, De Vrieze J, Kasmi S, Choteschovsky N, Klefenz A, Medina-Montano C, Winterwerber P, Chen C, Bros M, Lienenklaus S, Sanders NN, Koynov K, Schuppan D, Lambrecht BN, David SA, De Geest BG, Nuhn L
- Issue date: 2021 Jul 7
- Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles.
- Authors: Wang B, Van Herck S, Chen Y, Bai X, Zhong Z, Deswarte K, Lambrecht BN, Sanders NN, Lienenklaus S, Scheeren HW, David SA, Kiessling F, Lammers T, De Geest BG, Shi Y
- Issue date: 2020 Jul 15