We propose to develop a commercial product and procedure for the photothermal ablation of melanoma, including metastases, using targeted, near-infrared absorbing nanoparticles illuminated using a percutaneous laser energy delivery. This approach has been successfully demonstrated in a mouse model, and this proposal will extend the proof of feasibility into a spontaneous melanoma pig model. If successful , the Phase II proposal would conduct the necessary preclinical, in vitro and laboratory studies for an Investigational Device Exemption filing with FDA. Melanoma is characterized by a high capacity for invasion and metastasis. In-transit metastases, lymph node metastases, and brain metastases are serious problems in patients with this disease. Despite the application of various treatment approaches for in-transit metastases and brain metastases, the rate of treatment failure remains high. There is a critical need for innovative, minimally invasive techniques that can successfully target and treat metastatic lesions,while exerting minimal effects on surrounding normal tissue.