Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy.
Psoriasis
/ drug therapy
Animals
Inflammasomes
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Mice
Humans
Nanotubes
/ chemistry
Polymers
/ chemistry
Nanoparticles
/ chemistry
Reactive Oxygen Species
/ metabolism
Disease Models, Animal
Lipids
/ chemistry
Macrophages
/ drug effects
Caspase 1
/ metabolism
Female
Male
Liposomes
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Oct 2024
19 Oct 2024
Historique:
received:
03
03
2024
accepted:
11
10
2024
medline:
20
10
2024
pubmed:
20
10
2024
entrez:
19
10
2024
Statut:
epublish
Résumé
Localized delivery of inflammasome inhibitors in phagocytic macrophages could be promising for psoriasis treatment. The present work demonstrates the development of non-spherical lipid nanoparticles, mimicking pathogen-like shapes, consisting of an anti-inflammatory inflammasome inhibiting lipid (pyridoxine dipalmitate) as a trojan horse. The nanorods inhibit inflammasome by 3.8- and 4.5-fold compared with nanoellipses and nanospheres, respectively. Nanorods reduce apoptosis-associated speck-like protein and lysosomal rupture, restrain calcium influx, and mitochondrial reactive oxygen species. Dual inflammasome inhibitor (NLRP3/AIM-2-IN-3) loaded nanorods cause synergistic inhibition by 21.5- and 59-folds compared with nanorods and free drug, respectively alongside caspase-1 inhibition. The NLRP3/AIM-2-IN-3 nanorod when transformed into a polymeric scaffold, simultaneously and effectively inhibits RNA levels of NLRP3, AIM2, caspase-1, chemokine ligand-2, gasdermin-D, interleukin-1β, toll-like receptor 7/ 8, and IL-17A by 6.4-, 1.6-, 2.0-, 13.0-, 4.2-, 24.4-, 4.3-, and 1.82-fold, respectively in psoriatic skin in comparison to Imiquimod positive control group in an in-vivo psoriasis-like mice model.
Identifiants
pubmed: 39426974
doi: 10.1038/s41467-024-53396-x
pii: 10.1038/s41467-024-53396-x
doi:
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Polymers
0
Reactive Oxygen Species
0
Lipids
0
Caspase 1
EC 3.4.22.36
Nlrp3 protein, mouse
0
Lipid Nanoparticles
0
Liposomes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9035Subventions
Organisme : National Science Foundation (NSF)
ID : 2142917
Organisme : National Science Foundation (NSF)
ID : DMR1905559
Organisme : American Cancer Society (American Cancer Society, Inc.)
ID : RSG-19-009-01-CDD
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : T32GM139789
Informations de copyright
© 2024. The Author(s).
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