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

Tianshu Li, Jieyan He, Gabor Horvath, Tomasz Próchnicki, Eicke Latz, Shinji Takeoka

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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., the NLRP3 inflammasome activation of human macrophages and THP-1 cells, was evaluated by the detection of IL-1β 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 the 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.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number2
DOIs
Publication statusPublished - 2018 Feb 1

Keywords

  • Cationic liposomes
  • Il-1β
  • Lysine
  • Lysosome rupture
  • NLRP3 inflammasome activation

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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