Monovalent Antibody-Conjugated Lipid-Polymer Nanohybrids for Active Targeting to Desmoglein 3 of Keratinocytes to Attenuate Psoriasiform Inflammation

The study developed monovalent antibody-conjugated lipid-polymer nanohybrids (DPNPs) targeting desmoglein 3 on keratinocytes to treat psoriasiform inflammation. These nanohybrids, loaded with the PDE4 inhibitor AN2728, showed a 9-fold increase in keratinocyte uptake compared to non-targeted nanoparticles. In a psoriasis-like mouse model, the targeted nanohybrids significantly reduced skin inflammation, decreased epidermal thickness from 191 to 42 µm, and lowered the Psoriasis Area Severity Index by 74%. The DPNPs effectively restored skin barrier function, normalized chemokine levels, and demonstrated superior performance over free AN2728 and non-targeted nanoparticles in reducing inflammation and keratinocyte proliferation, highlighting their potential as a safe and efficient treatment for psoriasis.