2. Academic Validation
  3. Enhanced Cuproptosis via Metabolic Reprogramming Using Copper-Delivering Co-N-C Single-Atom Nanozyme

Enhanced Cuproptosis via Metabolic Reprogramming Using Copper-Delivering Co-N-C Single-Atom Nanozyme

  • ACS Nano. 2025 Jun 24;19(24):21969-21982. doi: 10.1021/acsnano.5c00012.
Kang Kim 1 2,  Jaewoo Lee 1 2,  Ok Kyu Park 1 3,  Hyochul Lee 3 4,  Taekyu Jang 3 4,  Jungho Kim 5,  Bowon Lee 1 2,  Jeong Hyun Kim 1 2,  Jaeho Moon 1 2,  Seoin Back 6 7,  Nohyun Lee 8,  Seung Hong Choi 1 3,  Taeghwan Hyeon 1 2
Affiliations

Affiliations

  • 1 Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.
  • 2 School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.
  • 3 Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
  • 4 Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
  • 5 Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 04107, Republic of Korea.
  • 6 KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea.
  • 7 Department of Integrative Energy Engineering, Korea University, Seoul 02841, Republic of Korea.
  • 8 School of Advanced Materials Engineering, Kookmin University, Seoul 02707, Republic of Korea.
PMID: 40499169 DOI: 10.1021/acsnano.5c00012
Abstract

Cuproptosis, a copper-dependent cell death, has shown promise as a Cancer therapy characterized by mitochondrial protein aggregation. However, this distinct feature makes its efficacy highly dependent on the metabolic state of Cancer cells, yielding poor outcomes in hypoxic tumors with a reduced mitochondrial activity. Herein, we construct a Cu-delivering vehicle with catalase-like activity using oxygen-rich cobalt single-atom nanozymes (Cu@CoNC(O)) to reprogram metabolism while delivering copper. By introduction of oxygen-containing functional groups onto carbon supports, Cu@CoNC(O) exhibits significantly improved loading efficiency of Cu ions compared to its oxygen-deficient counterpart. Simultaneously, the outstanding catalase-like activity of Cu@CoNC(O) alleviates hypoxia, switching metabolism from glycolysis to mitochondrial respiration through the inhibition of lactate metabolism and activation of the pyruvate dehydrogenase complex. The synergistic effect of the metabolic shift and efficient Cu delivery promotes Cuproptosis even under hypoxic conditions, leading to enhanced therapeutic effects. This study demonstrates the potential of single-atom nanozymes as catalytic ion delivery vehicles capable of concurrently performing catalytic functions and delivering metal ions, presenting an effective strategy to enhance Cuproptosis through metabolic modulation.

Keywords

catalase-like activity; cuproptosis; hypoxia relief; ion delivery; metabolic reprogramming; single-atom nanozymes.

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