Cationic lipid nanocarriers activate Toll-like receptor 2 and NLRP3 inflammasome pathways

Nanomedicine. 2014 May;10(4):775-82. doi: 10.1016/j.nano.2013.12.003. Epub 2013 Dec 20.


We provide evidence that cationic lipids, usually considered as a safe alternative to viral vectors as nanocarriers for gene therapy or drug intracellular delivery, do not behave as inert material but do activate cellular signalling pathways implicated in inflammatory reactions. We show here that the cationic lipid RPR206252 induces NF-κB activation, and the production of TNF-α, IL-1β, IL-6 and IFN-γ by human or mouse macrophage cell lines. Further, we demonstrate that the activation of inflammatory cascades by RPR206252 is dependent on Toll-like receptor 2 (TLR2), the natural sensor of bacterial lipopeptides and NOD-like receptor protein 3 (NLRP3), the major inflammasome component. Our results suggest that cationic lipid nanocarriers because of their ability to stimulate the innate system can be used as a new class of synthetic and safe adjuvant for vaccination.

From the clinical editor: Cationic lipid nanocarriers are typically considered neutral tools for gene delivery. However, as demonstrated in this study, they possess a clear ability to stimulate the innate immune system, and actually can be used as a new class of synthetic and safe adjuvant for vaccination.

Keywords: Cationic lipids; Immunostimulatory properties; Innate system; NLRP3; Toll-like receptor 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / immunology*
  • Cytokines / immunology
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology*
  • HEK293 Cells
  • Humans
  • Immunity, Innate / drug effects
  • Lipids / chemistry
  • Lipids / pharmacology*
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nanoparticles*
  • Toll-Like Receptor 2 / immunology*


  • Carrier Proteins
  • Cytokines
  • Drug Carriers
  • Lipids
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Nlrp3 protein, mouse
  • TLR2 protein, human
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2