Ferric Ion Driven Assembly of Catalase‐like Supramolecular Photosensitizing Nanozymes for Combating Hypoxic Tumors

Abstract A facile approach to assemble catalase‐like photosensitizing nanozymes with a self‐oxygen‐supplying ability was developed. The process involved Fe 3+ ‐driven self‐assembly of fluorenylmethyloxycarbonyl (Fmoc)‐protected amino acids. By adding a zinc(II) phthalocyanine‐based photosensitizer (ZnPc) and the hypoxia‐inducible factor 1 (HIF‐1) inhibitor acriflavine (ACF) during the Fe 3+ ‐promoted self‐assembly of Fmoc‐protected cysteine (Fmoc‐Cys), the nanovesicles Fmoc‐Cys/Fe@Pc and Fmoc‐Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly. The released Fe 3+ could catalyze the transformation of H 2 O 2 enriched in cancer cells to oxygen efficiently, thereby ameliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc‐Cys/Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc‐Cys/Fe@Pc, demonstrating the synergistic effect of ZnPc and ACF.