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Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small‐Molecule TLR7/8 Agonists
Author(s) -
De Vrieze Jana,
Louage Benoit,
Deswarte Kim,
Zhong Zifu,
De Coen Ruben,
Van Herck Simon,
Nuhn Lutz,
Kaas Frich Camilla,
Zelikin Alexander N.,
Lienenklaus Stefan,
Sanders Niek N.,
Lambrecht Bart N.,
David Sunil A.,
De Geest Bruno G.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201905687
Subject(s) - immune system , tlr7 , chemistry , amphiphile , inflammation , small molecule , innate immune system , biochemistry , microbiology and biotechnology , biology , immunology , polymer , copolymer , toll like receptor , organic chemistry
Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small‐molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum‐protein‐binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph‐node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.