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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.
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.
Afiliação
  • De Vrieze J; Department of Pharmaceutics, Ghent University, Ghent, Belgium.
  • Louage B; Department of Pharmaceutics, Ghent University, Ghent, Belgium.
  • Deswarte K; Department of Internal Medicine and Pediatrics, Ghent University, VIB Center for Inflammation Research, Ghent, Belgium.
  • Zhong Z; Department of Nutrition, Genetics and Ethology, Ghent University, Merelbeke, Belgium.
  • De Coen R; Department of Pharmaceutics, Ghent University, Ghent, Belgium.
  • Van Herck S; Department of Pharmaceutics, Ghent University, Ghent, Belgium.
  • Nuhn L; Max Planck Institute for Polymer Research, Mainz, Germany.
  • Kaas Frich C; Department of Chemistry, Aarhus University, Aarhus C, Denmark.
  • Zelikin AN; Department of Chemistry, Aarhus University, Aarhus C, Denmark.
  • Lienenklaus S; Institute for Laboratory Animal Science and Institute of Immunology, Hanover Medical School, Hannover, Germany.
  • Sanders NN; Department of Nutrition, Genetics and Ethology, Ghent University, Merelbeke, Belgium.
  • Lambrecht BN; Department of Internal Medicine and Pediatrics, Ghent University, VIB Center for Inflammation Research, Ghent, Belgium.
  • David SA; Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • De Geest BG; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Angew Chem Int Ed Engl ; 58(43): 15390-15395, 2019 10 21.
Article em En | MEDLINE | ID: mdl-31397948
ABSTRACT
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptor 7 Toll-Like / Receptor 8 Toll-Like / Imunidade Inata Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptor 7 Toll-Like / Receptor 8 Toll-Like / Imunidade Inata Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article