Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress
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Le résumé fourni par la source
Psoriasis is a chronic skin disorder characterized by dysregulation of immune and epithelial cells, resulting in persistent symptoms such as erythema, scaling, and induration. The abnormal metabolism and increased oxidative stress in psoriasis lesions have been identified as key drivers in the pathogenesis of psoriasis, forming a positive feedback loop within psoriatic skin. Therefore, targeting this feedback loop through modulation of local metabolism and alleviation of oxidative stress could be a rational and promising therapeutic strategy for addressing psoriasis. Herein, we designed a carrier-free nanomedicine (BTN) incorporating bilirubin (BR) and triptolide (TPL) to specifically target two key pathological features of psoriasis: inflammation induced by enhanced reactive oxygen species (ROS) and aberrant proliferation/immune activation driven by heightened nutrient metabolism. In vitro studies demonstrated that BTN effectively improved the water solubility of BR and TPL while facilitating efficient drug delivery to inflammatory keratinocytes. Mechanistically, BTN was found to alleviate the inflammatory cascade caused by oxidative stress and inhibit the IL-23/IL-17 axis. Importantly, downregulation of HIF-1α in keratinocytes resulted in blocking glucose transportation via GLUT-1 as well as amino acid transportation via LAT1, ultimately impeding excessive proliferation by disrupting nutritional requirements. In an imiquimod-induced psoriasis model, BTN effectively permeated inflamed skin epithelium with long-term retention effect. As a multifunctional nanomedicine combining ROS scavenging properties with regulation of nutrition metabolism, BTN shows great promise for reducing inflammatory cell infiltration and suppressing keratinocyte proliferation. Our findings demonstrated the great potential of BTN in ameliorating psoriasis symptoms by restoring the metabolic imbalance and mitigating oxidative stress between the epithelial and immune compartments.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Breaking the psoriasis pathological signaling cycle: A novel nanomedicine strategy targeting metabolism and oxidative stress
- Date Crossref
- 01/06/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The First People's Hospital of Wenling pays non établi dans la noticeÉtablissement de santé
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Wenzhou Medical University Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University pays non établi dans la noticeÉtablissement de santé
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Nanjing Drum Tower Hospital pays non établi dans la noticeÉtablissement de santé
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Affiliated Hospital of Jining Medical University pays non établi dans la noticeÉtablissement de santé
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Jinzhou Medical University Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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The Affiliated Hospital of Nanjing University Medical School Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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School of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
The First People's Hospital of Wenling, Department of Pediatrics — Wenzhou Medical University et Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.