Cu-Phytic acid Nanozyme-Induced Cuproptosis Therapy for Inhibition of Tumor Growth

Cuproptosis has recently received much attention in cancer treatment. However, copper ionophores don’t show the obvious clinical efficacy. Although some Cu-based and copper ionophores-loaded nanomaterials have been applied to induce cuproptosis, it is difficult to achieve the clinical translation limited by the complicated composition, harsh synthesis condition, external stimulus, and potential biotoxicity. Phytic acid, a naturally occurring organic phosphorus carbohydrate, possesses distinct antineoplastic effect on multiply types of cancer and high biocompatibility. Based on metal-phosphonate coordination, a novel Cu-phytic acid nanozyme (denoted as CP) with pH/GSH dual-response was fabricated by a “one-spot” method. CP with three enzyme-mimicking activities enhanced cuproptosis therapy through GSH depletion, reactive oxygen species augment, hypoxia relief and the attenuation of glycolysis. As a proof of concept, Elesclomol (a copper ionophore)-resistant A549 cells were used to investigate CP- induced cuproptosis for inhibition of tumor growth in vitro and in vivo.