Microneedle Patch Integrated with Porous Silicon Confined Dual Nanozymes for Synergistic and Hyperthermia‐Enhanced Nanocatalytic Ferroptosis Treatment of Melanoma

Abstract Superficial melanoma is the deadliest form of skin cancer without desirable clinically therapeutic options. Nanozymes, artificial nanomaterials with physicochemical performance and enzyme catalytic properties, have attracted considerable attention for antitumor therapy. However, the therapeutic efficiency of nanozymes is vulnerable to the tumor microenvironment (TME) and delivery process. Herein, a microneedle (MN) patch that integrates porous silicon (PSi) loaded with dual nanozymes is devised to bidirectionally regulate TME and accurately deliver nanocomplex to initiate ferroptosis for melanoma treatment. Benefitting from the channel confinement effect of PSi, the copper‐doped graphene quantum dots and palladium nanoparticles coloaded PSi (CuGQD/PdNPs@PSi) exhibit synergistic effect with enhanced mimicking peroxidase and glutathione oxidase activities, which are ≈2–3‐fold higher than those of monoconfined nanozyme or nonconfined nanozyme complexes. Additionally, the synergistic catalytic performance of CuGQD/PdNPs@PSi can be improved via photostimuli hyperthermia. The CuGQD/PdNPs@PSi can induce ferroptosis manifested by upregulation of lipid peroxides and inactivation of glutathione peroxidase 4. Furthermore, loading of nanocomplexes into MNs for administration resulted in a satisfactory melanoma growth inhibition of 98.8% within 14 days. Therefore, MNs encapsulated with CuGQD/PdNPs@PSi can provide a potentially nanocatalytic strategy for ferroptosis‐inducing tumor treatment while also meeting the medical needs of eradicating superficial tumors.