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

ABSTRACT: 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@MoS₂ 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.

SUBMITTER: Duan W 

PROVIDER: S-EPMC12376522 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature