Anti-inflammatory effect of metallic silver and gold nanoparticles complexed with polyphenolic compounds in human chronic stationary plaque psoriasis
Auch gedruckt in der BibliothekW: W-H 14.694
InstitutionUKU. Klinik für Hals-, Nasen- und Ohrenheilkunde
UKU. Klinik für Dermatologie und Allergologie
Ressourcen- / MedientypDissertation, Text
Datum der Erstveröffentlichung2016-05-18
Pro-inflammatory cytokines (TNFα, IL-12) represent key mediators of the pathogenesis in human psoriasis and constitute first-line targets of effective therapeutic strategies. Modern systemic therapies effectively target TNFα and IL-12 in psoriasis, but their use is hampered by immunosuppression-related side effects. As opposed to systemic side effects of currently employed biologics, selective inhibition of pro-inflammatory M1-macrophages in psoriasis skin lesions by topical drug delivery has not been reported so far. New biomaterials based on nanoparticles (NPs) carrying polyphenols-rich extracts of Cornus mass recently showed promising anti-inflammatory activity. Our research group aims at understanding how topically delivered silver and gold nanoparticles (Ag-NPs-CM, Au-NPs-CM) conditioned with Cornus mas modulate inflammation in psoriasis at cellular and molecular level. In patients, nanoparticles complexed with Cornus mas significantly improved the clinical appearance, with significant reduction of the PASI score after 6 weeks of topical treatment and significantly diminished the inflammatory infiltrate in psoriasis plaques as assessed by high-frequency ultrasonography. Incubation of pro-inflammatory stimulated murine macrophages with nanoparticles resulted in significantly decreased release of NO as well as of the pro-inflammatory cytokines IL-12 and TNFα as compared with non-treated macrophages. Immunofluorescence studies confirmed that nanoparticles significantly reduced the numbers of CD68-positive macrophages and their IL-12 and TNFα production in human psoriasis plaques. Moreover, NPs-CM appear to directly repress NFkappaB activation in macrophages, inhibiting the production of pro-inflammatory factors (TNFα, IL-12) with causal role in psoriasis pathogenesis. Ag and Au NPs-CM represent a novel nanoparticle-based ‘green’ technology which may provide a safe and efficient tool for modern psoriasis therapy, circumventing the immunosuppression-related side effects of biological therapies.