Near-Infrared-Light-Activated Nanoplatform for Vascular-Targeted Photodynamic Therapy in a Port-Wine-Stain Model

Port-wine stain (PWS) is a congenital capillary malformation in which ecstatic venules reside several millimeters beneath the epidermis, limiting the effectiveness of visible-light therapies that suffer from shallow penetration and significant photothermal deposition. To address these challenges, we engineered a UCNP@HMME nanoplatform that transduces near-infrared (NIR) light into visible emission to activate the photosensitizer hematoporphyrin monomethyl ether (HMME) at depth. In a vascular-rich chicken wattle model of PWS, we compared the therapeutic effect of UCNP@HMME-mediated NIR-PDT with visible-light-activated HMME-PDT. UCNP@HMME with 980 nm irradiation produced immediate purpura, progressive bleaching, and significant reductions in dermal capillaries with sustained antivascular effects. In contrast, 532 nm HMME-PDT achieved strong superficial bleaching but induced blistering and ulceration. Thermal profiling showed that 532 nm irradiation elevated blood temperature, whereas 980 nm irradiation did not measurably increase temperature, mitigating nonspecific thermal injury. These findings demonstrate that UCNP-mediated NIR activation decouples photochemical efficacy from epidermal heating, enabling deeper, safer, and more durable vascular photoablation in a PWS model.