Plant-derived Zerumbone and ICG Co-loaded Microneedle Patch System: A Novel Strategy for NIR-triggered Synergistic Chemo-Photothermal Therapy of Melanoma

Melanoma is an aggressive form of skin cancer arising from melanocytes, noted for its high metastatic potential and elevated mortality rate. Conventional treatment approaches are often limited by nonspecific systemic drug distribution, which can result in undesirable adverse effects and premature drug degradation. In this study, we report the development of a microneedle (MN)-mediated delivery platform, incorporating self-assembling polymeric micelles, combining a dissolvable MN patch with polymeric micelles designed to prevent ICG aggregation and co-encapsulate ZER and ICG, and enable combined chemotherapy and photothermal therapy against melanoma. These nanocarriers, referred to as ZER-ICG-polymer micelles, co-encapsulate Zerumbone (ZER)—a lipophilic sesquiterpenoid—and indocyanine green (ICG), a well-known photothermal agent. In vitro cytotoxicity assessments and intracellular distribution studies confirm a marked synergistic therapeutic effect under NIR light exposure, facilitating localized thermal ablation of melanoma cells. In vivo experiments using melanoma-bearing mice demonstrate that a single application of the ZER-ICG-loaded dissolvable microneedle patch, coupled with NIR irradiation, achieves potent photothermal performance and robust tumor growth inhibition, while inducing minimal systemic toxicity and negligible side effects. These findings highlight the promising potential of this transdermal delivery system for the treatment of superficial malignant tumors.