Bimetallic Plasmonic Nanozyme-Based Microneedle for Synergistic Ferroptosis Therapy of Melanoma.

Melanoma is the most common malignant skin tumor, characterized by complexity, invasiveness, and heterogeneity. Conventional therapies often yield poor outcomes, posing significant clinical challenges. Here, a microneedle (MN) patch that integrates nanozyme and traditional Chinese medicine (TCM) for ferroptosis pathway-dependent combined therapy of melanoma is designed. To amplify therapeutic activity, a novel Au@MoS bimetallic plasmonic nanozyme (BPNzyme) is prepared through a simple aqueous synthesis strategy involving a two-step process. Owing to the synergy between heterostructures, this rationally designed BPNzyme exhibits significantly enhanced therapeutic characteristics, including near-infrared (NIR) photothermal effect, peroxidase-like activity, and glutathione peroxidase-like property, which can effectively reshape the tumor microenvironment and disrupt the redox homeostasis. Under the combined action of the TCM β-elemene (β-ELE) and NIR light, further enhancement of oxidative damage, lipid peroxidation, and glutathione peroxidase 4 expression downregulation are observed for skin tumor cells, validating the synergistic amplification of ferroptosis. Moreover, the transdermal delivery of BPNzyme and β-ELE using the soluble hyaluronic acid MN patch effectively achieves 99.8% tumor growth suppression without significant systemic toxicity in vivo. These findings highlight the potential of the rationally designed BPNzyme-based MN system as a promising innovative strategy for non-invasive, efficient, and safe combination therapy of melanoma.