Skin-permeable FeSA-BN nanozyme for efficient transdermal inhibition and immunotherapy of melanoma.

Classical Mohs surgery and chemotherapy for metastatic melanoma treatment face limitations due to low efficacy and systemic toxicity, as they do not effectively exploit the tumor's superficial nature. We propose an iron single-atom-loaded boron nitride (FeSA-BN) nanozyme for non-invasive transdermal treatment of melanoma. The FeSA-BN features Fe-N3 coordination via iron atoms anchored at boron vacancies, which enhance endogenous hydrogen peroxide conversion into hydroxyl radicals for potent antitumor activity. With an average size of only ∼8 nm, the FeSA-BN nanozymes enable efficient transdermal delivery, achieving a remarkable 93 % suppression rate of B16F10 melanoma. Additionally, they triggered robust immunity against both primary and distant tumors. This transdermal delivery approach combines high therapeutic efficacy with minimal invasiveness, circumventing systemic side effects by leveraging melanoma's accessible location. This work provides a non-invasive strategy by integrating localized nanozymatic treatment and immune activation, offering a safer, effective alternative to conventional melanoma treatments.