Upconversion-Mediated Phototherapy for Psoriasis Treatment.

Psoriasis is a chronic, relapsing, immune-mediated systemic inflammatory disease that affects 2-3% of the global population. It affects the skin and leads to complications in multiple systems, severely impacting patients' quality of life. Although traditional topical therapies, systemic treatments, phototherapy, and emerging biological treatments have progressed in treating psoriatic dermatitis, they still cannot cure psoriasis and are associated with multiple side effects, including infections and phototoxicity. Building upon conventional narrowband ultraviolet B (NB-UVB) phototherapy, our research utilized upconversion nanoparticles (UCNPs) for in vivo phototherapy in the treatment of psoriasis. When taken up by macrophages, under 808 nm near-infrared (NIR) light with better tissue penetration, the UV light at 365 nm and blue light at 475 nm emitted by UCNPs could potentially modulate opsin 3, inhibiting pro-inflammatory (M1) macrophage (marked by IL-1β, iNOS, TNF-α, IL-23, IL-17A) and promoting anti-inflammatory (M2) macrophage (marked by Fizz 1 and Arginase 1), indicating that UCNPs-mediated phototherapy could switch psoriasis macrophages from M1 to M2. Transcriptomic profiling further revealed that this phototherapy reverses the IL‑23-induced psoriatic phenotype in RAW264.7 macrophages by upregulating M2‑related gene expression while downregulating key inflammatory effectors, which significantly improves psoriasis-like dermatitis without causing phototoxicity, highlighting the potential of phototherapy for psoriasis.