Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer-Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists.
Jana De VriezeBenoit LouageKim DeswarteZifu ZhongRuben De CoenSimon Van HerckLutz NuhnCamilla Kaas FrichAlexander N ZelikinStefan LienenklausNiek N SandersBart N LambrechtSunil A DavidBruno G De GeestPublished in: Angewandte Chemie (International ed. in English) (2019)
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.