Heterostructures with Built-in Electric Fields for Long-lasting Chemodynamic Therapy

Sustained signal activation by hydroxyl radicals (⋅OH) has great significance, especially for tumor treatment, but remains challenging. Here, a built-in electric field (BIEF)-driven strategy was proposed for sustainable generation of ⋅OH, thereby achieving long-lasting chemodynamic therapy (LCDT). As a proof of concept, a novel Janus-like Fe@Fe₃O₄−Cu₂O heterogeneous catalyst was designed and synthesized, in which the BIEF induced the transfer of electrons in the Fe core to the surface, reducing ≡Cu²⁺ to ≡Cu⁺, thus achieving continuous Fenton-like reactions and ⋅OH release for over 18 h, which is approximately 12 times longer than that of Fe₃O₄−Cu₂O and 72 times longer than that of Cu₂O nanoparticles. In vitro and in vivo antitumor results indicated that sustained ⋅OH levels led to persistent extracellular regulated protein kinases (ERK) signal activation and irreparable oxidative damage to tumor cells, which promoted irreversible tumor apoptosis. Importantly, this strategy provides ideas for developing long-acting nanoplatforms for various applications.