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.

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Keywords immunomodulation, innate immunity, lipid amphiphiles, lymph nodes, polymers
Persistent URL dx.doi.org/10.1002/anie.201905687, hdl.handle.net/1765/120256
Journal Angewandte Chemie (International ed. in English)
De Vrieze, J. (Jana), Louage, B. (Benoit), Deswarte, K, Zhong, Z. (Zifu), De Coen, R. (Ruben), Van Herck, S. (Simon), … De Geest, B.G. (Bruno G.). (2019). Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer-Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists. Angewandte Chemie (International ed. in English), 58(43), 15390–15395. doi:10.1002/anie.201905687