Please use this identifier to cite or link to this item: http://hdl.handle.net/10773/36127
Title: Macrophage-targeted shikonin-loaded nanogels for modulation of inflammasome activation
Author: Cardoso, Matias
Gaspar, Vítor M.
Ferreira, Carolina
Silvestre, Ricardo
Duarte, Iola F.
Mano, João F.
Keywords: Interleukin-1beta
Macrophages
NLR Family, Pyrin Domain-Containing 3 Protein
Nanogels
Naphthoquinones
Inflammasomes
Zein
Issue Date: Jun-2022
Publisher: Elsevier
Abstract: 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 CD163highHLA-DRlow 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.
Peer review: yes
URI: http://hdl.handle.net/10773/36127
DOI: 10.1016/j.nano.2022.102548
ISSN: 1549-9634
Appears in Collections:CICECO - Artigos

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