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 |
Files in This Item:
File | Description | Size | Format | |
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Cardoso2022_Nanomedicine.pdf | 3.07 MB | Adobe PDF |
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