Utilize este identificador para referenciar este registo:
http://hdl.handle.net/10773/36127
Título: | Macrophage-targeted shikonin-loaded nanogels for modulation of inflammasome activation |
Autor: | Cardoso, Matias Gaspar, Vítor M. Ferreira, Carolina Silvestre, Ricardo Duarte, Iola F. Mano, João F. |
Palavras-chave: | Interleukin-1beta Macrophages NLR Family, Pyrin Domain-Containing 3 Protein Nanogels Naphthoquinones Inflammasomes Zein |
Data: | Jun-2022 |
Editora: | Elsevier |
Resumo: | 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 |
Aparece nas coleções: | CICECO - Artigos |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Cardoso2022_Nanomedicine.pdf | 3.07 MB | Adobe PDF |
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