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Lipid Nature and Alkyl Length Influence Lymph Node Accumulation of Lipid‐Polyethylene Glycol Amphiphiles
Author(s) -
De Vrieze Jana,
Baptista Antonio P.,
Nuhn Lutz,
Van Herck Simon,
Deswarte Kim,
Yu Haijun,
Lambrecht Bart N.,
De Geest Bruno G.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100079
Subject(s) - amphiphile , chemistry , peg ratio , context (archaeology) , immune system , polyethylene glycol , biochemistry , biology , immunology , organic chemistry , copolymer , paleontology , finance , economics , polymer
Immunomodulatory drugs are of great relevance in the context of vaccine delivery and cancer immunotherapy. Due to the ubiquitous presence of immune cells throughout the body, gaining control over the biodistribution and activity of such drugs is crucial to limit off‐target inflammatory responses. Here, the authors report on lipid‐PEG (polyethylene glycol) amphiphiles as well‐defined amphiphilic carries for lymph node targeted delivery. Comparing cholesterol and dialkyl lipids with different alkyl chain length, the authors found that both the nature of the lipid, as well as, the alkyl chain length have a dramatic influence on cellular uptake and lymph node translocation. Whereas shorter dioctyl‐PEG amphiphiles show overall poor performance, larger dioctadecyl‐PEG amphiphiles are prone to solubility issues. Didodecyl‐PEG amphiphiles with intermediate alkyl chain length are on par with cholesteryl‐PEG amphiphiles in in vitro and in vivo cellular uptake and lymphoid tissue targeting. Immunization with a cholesteryl‐PEG‐imidazoquinoline (TLR7/8 agonist) amphiphile‐adjuvanted model antigen shows induction of immune responses that are qualitatively different from Montanide‐adjuvanted antigen, characterized by effector CD8 + T cells with immediate cytotoxic potential and robust IgG2 antibody responses. These findings provide a rational base for further adjuvant design based on the type of immunity needed for a specific vaccination or therapeutic setting.