摘要
Cutaneous melanoma is highly metastatic and deadly, with conventional therapies often proving ineffective while causing significant side effects. Cerium-based metal-organic frameworks (Ce-MOFs) and their derivatives have recently attracted attention in antitumor therapy due to their unique physicochemical properties and multi-enzyme-mimicking activities. However, their catalytic efficiency remains suboptimal because of challenges such as ambiguous active sites and low utilization efficiency of metal ions. Their therapeutic efficacy is also frequently hampered by inefficient delivery systems. Here, a microneedle (MN) patch-assisted transdermal delivery system of oxygen vacancy-rich cerium‑iron bimetallic organic framework (CeFe-MOFs) derivatives (CeFeO x ) is constructed for synergistic chemodynamic (CDT) and starvation therapy against melanoma. Compared with Ce-MOFs derivatives (CeO x ), CeFeO x exhibits superior peroxidase-like (POD-like) activity, which may be attributed to Fe doping increasing the Ce 3+ /Ce 4+ ratio and, consequently, the concentration of oxygen vacancies. Through theoretical calculations, the catalytic pathway of CeFeO x toward H 2 O 2 and the mechanism by which Fe doping enhances the POD-like activity of CeO x are further revealed. The results indicate that the enhanced POD-like activity of CeFeO x originates from local changes in the electronic structure of the cerium lattice induced by Fe doping, which reduces the activation energy of key reaction steps. Meanwhile, Fe doping promotes the adenosine triphosphate (ATP) hydrolysis ability of CeO x , which is attributed to the strong binding affinity between Fe 3+ and ATP. The MN patch penetrates the stratum corneum, enabling efficient delivery of CeFeO x to intratumoral regions and thereby inducing melanoma cell death. Taken together, the MN-assisted cutaneous delivery system of CeFeO x provides a reasonable strategy for treating melanoma with highly enhanced catalytic activity.
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