Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists

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  • Jana De Vrieze, Universiteit Gent
  • ,
  • Benoit Louage, Universiteit Gent
  • ,
  • Kim Deswarte, Universiteit Gent
  • ,
  • Zifu Zhong, Universiteit Gent
  • ,
  • Ruben De Coen, Universiteit Gent
  • ,
  • Simon Van Herck, Universiteit Gent
  • ,
  • Lutz Nuhn, Max Planck Institute for Polymer Research
  • ,
  • Camilla Kaas Frich
  • ,
  • Alexander N. Zelikin
  • Stefan Lienenklaus, Hannover Medical School
  • ,
  • Niek N. Sanders, Universiteit Gent
  • ,
  • Bart N. Lambrecht, Universiteit Gent, Erasmus University Medical Center
  • ,
  • Sunil A. David, University of Minnesota
  • ,
  • Bruno G. De Geest, Universiteit Gent

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.

OriginalsprogEngelsk
TidsskriftAngewandte Chemie - International Edition
Vol/bind58
Nummer43
Sider (fra-til)15390-15395
Antal sider6
ISSN1433-7851
DOI
StatusUdgivet - okt. 2019

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