Skin Cancer Treatment with Subcutaneous Delivery of Doxorubicin-Loaded Gelatin Nanoparticles and NIR Activation

Subcutaneous (SC) administration of chemotherapeutics combined with near-infrared (NIR) light activation can effectively target skin tumors by triggering localized drug release and enhancing cytotoxic effects. In this study, we developed NIR-responsive indocyanine green (ICG) and the chemotherapeutic agent doxorubicin (Dox) loaded into gelatin nanoparticles (NPs) for SC delivery in a skin tumor-bearing mouse model. Histological examination (hematoxylin and eosin staining) confirmed the successful delivery and swelling behavior of the Dox/ICG-loaded gelatin NPs at the SC site. In vitro and in vivo experiments demonstrated that NIR activation of the Dox/ICG-loaded gelatin NPs generated significant photothermal heat (48 and 46 °C), leading to targeted drug release and a substantial reduction in skin tumor size (from 15 to 3 mm³). Our findings suggest that this dual-modality approach of SC chemotherapeutic administration and NIR-triggered photothermal therapy can concentrate cytotoxic drugs at the tumor site, offering a promising strategy for improving skin cancer treatment.