Macrophage-Targeted Shikonin-Loaded Nanogels for Modulation of Inflammasome Activation.
Fiche publication
Date publication
mars 2022
Journal
Nanomedicine : nanotechnology, biology, and medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MANO João F.
Tous les auteurs :
Cardoso M, Gaspar VM, Ferreira C, Silvestre RS, Duarte IF, Mano JF
Lien Pubmed
Résumé
This study reports the formulation and delivery of Hyaluronic acid-Zein (HA-Zein) nanogels loaded with Shikonin (SK) to selectively attenuate macrophage inflammasome. The self-assembled nanogels, produced by nanoprecipitation, exhibited high encapsulation efficiency, and were selectively internalized by human THP-1-derived macrophages without eliciting cytotoxic responses. Cell treatment with HA-Zein-SK nanogels before stimulation with LPS and Nigericin significantly suppressed caspase-1 activation and IL-1β production, indicating inflammasome inhibition. Importantly, HA-Zein-SK nanogels bioinstructed inflammasome activated macrophages towards an anti-inflammatory CD163HLA-DR phenotype and led to a marked reduction in the release of pro-inflammatory mediators (TNF-α, IL-6 and IP-10). Extracellular metabolic profiling additionally revealed SK-mediated downregulation of cellular glycolytic activity, which was corroborated by a significant decrease of glycolytic genes transcription. All in all, our findings demonstrate the potential of bioactive SK-containing, self-assembled nanogels to modulate exacerbated responses in innate immune cells and, prospectively, in human tissues where NRLP3 inflammasome is abnormally activated upon injury or disease.
Mots clés
Immunometabolism, Inflammasome, Macrophages, Nanocarriers, Shikonin
Référence
Nanomedicine. 2022 Mar 14;:102548