Targeted delivery of adamantylated peptidoglycan immunomodulators in lipid nanocarriers: NMR shows that cargo fragments are available on the surface - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Physical Chemistry B Année : 2020

Targeted delivery of adamantylated peptidoglycan immunomodulators in lipid nanocarriers: NMR shows that cargo fragments are available on the surface

Résumé

We present an in-depth investigation of the membrane interactions of peptidoglycan (PGN)-based immune adjuvants designed for lipid-based delivery systems using NMR spectroscopy. The derivatives contain a cargo peptidoglycan (PGN) dipeptide fragment and an adamantyl group, which serves as an anchor to the lipid bilayer. Furthermore, derivatives with a mannose group that can actively target cell surface receptors on immune cells are also studied. We showed that the targeting mannose group and the cargo PGN fragment are both available on the lipid bilayer surface, thereby enabling interactions with cognate receptors. We found that the nonmannosylated compounds are incorporated stronger into the lipid assemblies than the mannosylated ones, but the latter compounds penetrate deeper in the bilayer. This might be explained by stronger electrostatic interactions available for zwitterionic nonmannosylated derivatives as opposed to the compounds in which the charged N-terminus is capped by mannose groups. The higher incorporation efficiency of the nonmannosylated compounds correlated with a larger relative enhancement in immune stimulation activities upon lipid incorporation compared to that of the derivatives with the mannose group. The chirality of the adamantyl group also influenced the incorporation efficiency, which in turn correlated with membrane-associated conformations that affect possible intermolecular interactions with lipid molecules. These findings will help in improving the development of PGN-based immune adjuvants suitable for delivery in lipid nanoparticles.
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Dates et versions

hal-03009687 , version 1 (17-11-2020)

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Rosana Ribić, Mateja Manček-Keber, Fernando Chain, Davy Sinnaeve, José C Martins, et al.. Targeted delivery of adamantylated peptidoglycan immunomodulators in lipid nanocarriers: NMR shows that cargo fragments are available on the surface. Journal of Physical Chemistry B, 2020, 124 (20), pp.4132-4145. ⟨10.1021/acs.jpcb.0c00029⟩. ⟨hal-03009687⟩
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