Synergistic Chemo-Photodynamic Therapy Based on Hollow Mesoporous Organosilica Nanoparticles for Treating Psoriasis-Like Inflammation

Psoriasis is a common chronic inflammatory and proliferative skin disease that is prone to recurrence, long course, and hard to cure. Currently, methotrexate (MTX)-based systematic treatment is the most widely used treatment regimen for psoriasis in clinical practice. Long-term oral administration of MTX has a plethora of side effects, including induced liver and kidney toxicity and even bone marrow suppression in severe cases. To reduce the incidence of adverse reactions, the topical application of nano-drug delivery systems by modifying MTX would be necessary. Here, we propose a chemo-photodynamic therapy strategy by preparing hollow mesoporous silica nanoparticles MTX@HMN-Ce6-HA containing MTX (loading: 78%) and chlorine e6 (Ce6) (loading: 80%), which generate ROS under light conditions, while the ROS contributes to the disulfide bond breakage in the silica nanoparticles to release MTX, and the encapsulated hyaluronic acid (HA) to increase the permeability of the nanomaterials, the efficacy was verified at the cellular and animal levels. MTX@HMN-Ce6@HA could significantly decrease HaCaT cell viability, induce cell apoptosis and reduce inflammation by regulating mitochondrial apoptosis pathway and STAT3-NF-κB p65 pathway. Importantly, this strategy synergistically treats psoriasis showing better therapeutic efficacy by combing MTX chemotherapy and Ce6 phototherapy. Overall, MTX@HMN-Ce6@HA exerted potent therapeutic efficacy against psoriasis-like skin inflammation without overt toxic signals, which could provide a theoretical basis and experimental support for the topical treatment of psoriasis.