Copper-Based Nanotubes That Enhance Starvation Therapy Through Cuproptosis for Synergistic Cancer Treatment

Hepatic cancer is the leading cause of worldwide death due to lack of effective chemotherapy drugs. Cuproptosis is a novel regulated cell death and offers a new potential mechanism to eliminate hepatic cancer. In this study, it is found that hepatocellular carcinoma (HCC), which is one of the hepatic cancer, is sensitive to cuproptosis by analysing clinical specimens and databases. Thus, a copper-based nanotube (NT) with copper ionophores to induce enhanced cuproptosis is designed. In combination with starvation therapy, the NT significantly inhibited energy metabolism in HCC cells. This results show that the depletion of GSH by Cu²⁺ intensified oxidative stress and cuproptosis, resulting in ROS generation and DLAT aggregation, indicating the enhancement of cuproptosis and the Fenton reaction. The NT with synergetic cuproptosis, the Fenton reaction and starvation therapy provide a valuable insight into the prospect of HCC treatment.