Functional nano-nucleic acid platform promotes copper-induced gastric cancer cell death

Abstract

The targeted design of nanomedicine has revolutionized tumor therapy. We report an all-in-one ZnO@DNAzyme-Cu(II)Elesclomol nanoplatform that synchronously silences ATP7B and escorts Cu²⁺ to evoke cuproptosis. The DNAzyme within the nanoparticle was independently designed to target ATP7B, a key regulator of cuproptosis. This multifunctional nanoplatform can be efficiently internalized by gastric cancer cells (SGC7901), where it undergoes degradation and releases its active components. ZnO NPs act as a reservoir for zinc ions, which facilitate the catalytic activity of DNAzyme, enabling it to target and suppress ATP7B mRNA expression. Additionally, ZnO NPs reduce intracellular glutathione (GSH) levels, enhance reactive oxygen species (ROS) production, and elevate oxidative stress in tumor cells. The subsequent release of Cu(II)-Elesclomol triggers copper-induced cell death. Both in vitro and in vivo experiments demonstrated that this nanoplatform effectively inhibits tumor progression and promotes tumor cell death. This proposed nanoplatform holds significant promise for multifunctional cancer therapy and personalized nanomedicine.