Photo-Controlled Treatment for Psoriasis-Like Skin Lesions by UVB-Photoactivated Hydrogen Sulfide Donors and Pterostilbene.

Smart and efficient drug delivery is always desirable, especially for chronic diseases, such as psoriasis. We developed an ultraviolet B (UVB) light-triggered scaffold, 1,4,2-dioxazol-5-thione (DOT), for the controlled release of hydrogen sulfide (H2S), a pivotal endogenous gaseous signaling molecule with promise for anti-inflammatory and antioxidant therapies. In the DOT scaffold, the kinetics for H2S release are efficiently tuned by fine-adjusting the electronic properties. Upon photoirradiation, DOT releases carbonyl sulfide (COS), which is rapidly converted to H2S by carbonic anhydrase (CA). Furthermore, the DOT platform is conjugated to the active pharmaceutical ingredient pterostilbene (PTE) to afford a hybrid prodrug, PTE-DOT. Under UVB irradiation at 308 nm, a standard wavelength for psoriasis phototherapy, PTE-DOT simultaneously released H2S and PTE, thereby exerting combined anti-inflammatory and antioxidant effects in vivo. In the psoriasis mouse model, PTE-DOT effectively reduced epidermal thickening and hyperkeratosis, suppressed the production of key psoriatic inflammatory cytokines, and inhibited the differentiation of Th17 cells in the spleen. Thus, the photo-controlled prodrug strategy provides a platform for designing smart drug delivery systems to ameliorate psoriasis-like skin inflammation.