Unlocking the potential of photodynamic therapy in Psoriasis: Mechanistic insights, wide-ranging applications, challenges and future directions

Abstract

Psoriasis is an autoimmune skin disorder involving the interaction of genetic factors and environmental stress which leads to uncontrolled proliferation of keratinocytes and activation of the immune system. Conventional treatment options, including topical therapies, phototherapy, systemic drugs, and biologics, are used based on disease severity. Recently, photodynamic therapy (PDT) has gained attention due to its unique advantages over traditional treatments. PDT relies on three key components i.e. photosensitizer (PS) administered either locally or systemically, specific light irradiation, and molecular oxygen to generate reactive oxygen species (ROS), leading to the damage of photoactivated cells through cellular apoptosis and necrosis. Recent studies have explored innovative PSs and delivery strategies to enhance the efficacy of PDT in psoriasis. Emerging research highlights the potential of PDT to suppress keratinocyte proliferation and modulate inflammatory pathways, such as JAK/STAT inhibition via ROS-mediated upregulation of SOCS1/3. Innovative delivery strategies and photosensitizers, including chlorin e6, IR820, ZnPc-F7, and 5-aminolevulinic acid (ALA), have been developed to enhance selectivity, reduce treatment-associated discomfort, and improve skin penetration. Nanocarrier systems, such as mesoporous silica nanoparticles, polydopamine-based platforms, and lipid-based nanocarriers, have enabled synergistic photochemotherapy and dual photothermal-photodynamic approaches, leading to improved therapeutic outcomes by inducing apoptosis, restoring skin barrier function, and attenuating proinflammatory signaling. This review highlights PDT principles, mechanisms, approved PSs, and emerging combinations. Despite its promising effects, PDT remains underutilized in psoriasis, demanding further research and nanotech-driven optimization for patient-friendly therapies.