4 years ago

Lysine-containing cationic liposomes activate NLRP3 inflammasome: effect of a spacer between the head group and the hydrophobic moieties of the lipids.

Eicke Latz, Tianshu Li, Gabor Horvath, Shinji Takeoka, Tomasz Próchnicki, Jieyan He
Cationic lipids containing lysine head groups and ditetradecyl, dihexadecyl or dioctadecyl glutamate hydrophobic moieties with/without propyl, pentyl or heptyl spacers were applied for the preparation of cationic liposomes using a simple bath type-sonicator. The size distribution, zeta potential, cellular internalization, and cytotoxicity of the liposomes were characterized, and the innate immune stimulation, e.g., NLRP3 inflammasome activation of human macrophages and THP-1 cells were evaluated by the detection of IL-1ß release. Comparatively, L3C14 and L5C14 liposomes, made from the lipids bearing lysine head groups, ditetradecyl hydrophobic chains and propyl or pentyl spacers, respectively, were the most potent to activate NLRP3 inflammasome. The possible mechanism includes endocytosis of the cationic liposomes and subsequent lysosome rupture without significant inducement of reactive oxygen species production. In summary, we first disclosed the structural effect of cationic liposomes on the NLRP3 inflammasome activation, which gives an insight into the application of nanoparticles for improved immune response.

Publisher URL: http://doi.org/10.1016/j.nano.2017.10.011

DOI: 10.1016/j.nano.2017.10.011

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