Potential of Nanoparticle-Based Phototherapies for Future Treatment of Uveal Melanoma

This review aims at exploring nanoparticle-based phototherapies of uveal melanoma (UM), the most common primary intraocular malignancy in adults with an estimated incidence of 5-7 cases per million individuals per year, a disproportionately high metastatic risk and poor prognosis in advanced stages. UM exhibits unique biological and anatomical features, including an immune-privileged ocular microenvironment, the blood-ocular barrier, and high melanin content, contributing to therapeutic complexity. Current treatments, including radiotherapy, surgery, and systemic therapies, achieve local tumor control but remain limited by adverse effects, recurrence, and insufficient efficacy against metastatic disease. Laser-based therapies, including transpupillary thermotherapy and photodynamic therapy, offer minimally invasive alternatives. However, their performance is constrained by limited light penetration, melanin-induced uneven absorption, and incomplete tumor eradication. Recent advances in nanotechnology offer opportunities to overcome these limitations. Nanoparticle-based phototherapies can improve tumor targeting, photosensitizer delivery, and localized activation while reducing off-target effects. Multifunctional nanoplatforms may combine imaging, drug delivery, and synergistic therapies such as immunotherapy or chemotherapy. Although promising preclinical results highlight improved tumor control and antitumor responses, challenges related to safety, biodistribution, and clinical translation remain. This review discusses these challenges and future directions for optimized nanoplatforms to improve disease management and metastasis prevention.