Autocatalytic Artesunate Coordinated ZIF-8 Nanoplatforms with Metal-Polyphenol Network Coating for Targeted Tumor Chemodynamic Therapy

Artesunate (Art) with a unique peroxy-bridging bond can react with a ferrous ion and produce excess carbon-centered radicals, which cause irreversible damage to tumor cells. However, the antitumor effect of artesunate still faces challenges due to its poor water solubility and insufficient amount of ferrous ions in tumor cells. Herein, we constructed artesunate coordinated zeolite imidazole framework nanoplatforms (Art/ZIF NPs) coated with ferric ion-rutin network (Ru–Fe@Art/ZIF NPs) for synergy therapy. In virtue of zinc-ion-mediated coordination, Art was efficiently loaded into ZIF-8 NPs (loading capacity and rate are 29.58 and 30.73%) and responsively released under an acidic environment. Meanwhile, the introduction of rutin (a type of plant flavonoid) not only enabled tumor targeting via GLUT receptors but also reduced Fe3+ to Fe2+ under acidic conditions. Subsequently, these ferrous ions loading with Art enhance the tumor killing effect via radical-dependent cell cycle arrest. This "core–shell" autocatalytic nanoplatform provides a novel strategy for developing Art-based chemodynamic therapy.