Synergistic chemo-photodynamic therapy based on hollow mesoporous organosilica nanoparticles for reducing psoriasis-like inflammation

Psoriasis is a prevalent chronic inflammatory and proliferative skin condition characterized by its tendency for recurrence, prolonged duration, and challenging treatment. The most commonly employed treatment approach in clinical practice involves methotrexate (MTX)-based systemic therapy. However, long-term oral intake of MTX is associated with numerous side effects, ranging from induced liver and kidney toxicity to severe cases of bone marrow suppression. To reduce the incidence of adverse reactions, the topical application of nano-drug delivery systems by modifying MTX might potentially prove beneficial. This study introduces a novel chemo-photodynamic therapy approach utilizing hollow mesoporous silica nanoparticles (MTX@HMN-Ce6-HA) loaded with methotrexate (MTX) (loading: 78 %) and chlorine e6 (Ce6) (loading: 80 %). These nanoparticles generate reactive oxygen species (ROS) under light conditions, which aid in breaking the disulfide bond in the silica nanoparticles to release MTX and encapsulated hyaluronic acid (HA), thereby enhancing the permeability of the nanomaterials. The efficacy of this approach was evaluated at both cellular and animal levels. MTX@HMN-Ce6@HA demonstrated significant reductions in HaCaT cell viability, induction of cell apoptosis, and inflammation reduction by modulating the mitochondrial apoptosis pathway and STAT3-NF-κB p65 pathway. Importantly, this strategy synergistically treats psoriasis showing enhanced therapeutic efficacy by combining MTX chemotherapy with Ce6 phototherapy. In summary, MTX@HMN-Ce6@HA demonstrated powerful therapeutic efficacy against psoriasis-like skin inflammation without displaying any noticeable toxic effects. This finding could serve as a theoretical foundation and experimental validation for the topical treatment of psoriasis.