Methotrexate (MTX) is an anti-proliferative drug used for treating inflammatory diseases including psoriasis. Systemic administration of MTX, however, is associated with dose-limiting side effects, and local therapy is impeded due to poor transdermal penetration.

Here, we used MTX coupled to skin-penetrating gold nanoparticles (GNPs) for targeted drug delivery and minimization of systemic side effects in two mouse models of psoriasis.

Systemic or topical MTX-GNPs were well-tolerated and demonstrated superior anti-inflammatory efficacy compared to conventional MTX in the imiquimod (IMQ)-induced mouse model. Topical MTX-GNPs diminished cutaneous inflammation by significantly reducing gd T cells, CD4⁺ T cells, and neutrophils.

In the human xenograft model, normal-appearing skin from psoriasis patients were transplanted onto the back of immunocompromised AGR mice and topically treated with MTX-GNPs, topical calcipotriol-betamethasone (TCB), or vaseline. Treatment with MTX-GNPs inhibited skin hyperplasia significantly better than TCB and led to profound tissue remodeling, highlighting that MTX-GNP's effects were not limited to immune cells but also involved stromal cells including keratinocytes and fibroblasts, as also evidenced by RNA sequencing.

In conclusion, MTX-GNPs potently inhibits psoriasis development in the studied models, suggesting a novel non-steroidal topical alternative in psoriasis.

Dr. Antonios G.A. Kolios, Department of Immunology, University Hospital Zürich, 8091 Zurich, Switzerland

Im Rahmen des Institutsseminars Biologische Chemie