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

Xuan Han; Xin Zhang; Zhiping Liu; Hang Liu; Derek Wu; Yinli He; Kexin Yuan; Yi Lyu; Xiaofei Liu

doi:10.1002/advs.202504121

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

Adv Sci (Weinh). 2025 Jun 5:e04121. doi: 10.1002/advs.202504121. Online ahead of print.

Authors

Xuan Han^{1

2}, Xin Zhang³, Zhiping Liu⁴, Hang Liu^{1

2}, Derek Wu⁵, Yinli He⁶, Kexin Yuan², Yi Lyu^{1

2

4}, Xiaofei Liu^{1

2

4}

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
² Center for Regenerative and Reconstructive Medicine, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
³ Department of Orthopedics, The Second Affiliated hospital of Air Force Medical University (AFMU), Xi'an, Shaanxi Province, 710000, China.
⁴ National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
⁵ Brooklyn College, the City University of New York, Brooklyn, NY, 11210, USA.
⁶ BioBank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.

PMID: 40470742
DOI: 10.1002/advs.202504121

Abstract

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.

Keywords: cuproptosis; hepatocellular carcinoma; starvation therapy.

Abstract

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