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Cofactors and Coenzymes01:27

Cofactors and Coenzymes

Enzymes require additional components for proper function. There are two such classes of molecules: cofactors and coenzymes. Cofactors are metallic ions and coenzymes are non-protein organic molecules. Both of these types of helper molecule can be tightly bound to the enzyme or bound only when the substrate binds.

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

Kang Kim1,2, Jaewoo Lee1,2, Ok Kyu Park1,3

  • 1Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.

ACS Nano
|June 11, 2025
PubMed
Summary
This summary is machine-generated.

This study developed a novel copper delivery system using cobalt nanozymes to enhance cancer cell death (cuproptosis), even in oxygen-poor tumors. The strategy reprograms cancer metabolism for improved therapeutic outcomes.

Keywords:
catalase-like activitycuproptosishypoxia reliefion deliverymetabolic reprogrammingsingle-atom nanozymes

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Biology

Background:

  • Cuproptosis, a copper-dependent cell death, is a promising cancer therapy but is limited by tumor hypoxia.
  • Hypoxic tumors exhibit reduced mitochondrial activity, hindering the efficacy of cuproptosis-inducing agents.

Purpose of the Study:

  • To develop a novel copper delivery vehicle with enhanced catalase-like activity to overcome hypoxia-induced resistance to cuproptosis.
  • To reprogram cancer cell metabolism for improved therapeutic outcomes.

Main Methods:

  • Construction of oxygen-rich cobalt single-atom nanozymes loaded with copper (Cu@CoNC(O)).
  • Evaluation of Cu@CoNC(O) for copper ion loading efficiency, catalase-like activity, and hypoxia alleviation.
  • Assessment of metabolic reprogramming, including lactate metabolism inhibition and pyruvate dehydrogenase complex activation.
  • Investigation of synergistic effects of metabolic shift and copper delivery on cuproptosis induction in hypoxic conditions.

Main Results:

  • Cu@CoNC(O) demonstrated superior copper loading efficiency compared to oxygen-deficient counterparts.
  • The nanozyme effectively alleviated tumor hypoxia and shifted cancer cell metabolism from glycolysis to mitochondrial respiration.
  • Synergistic effects of metabolic reprogramming and copper delivery significantly promoted cuproptosis, even under hypoxic conditions.
  • Enhanced therapeutic effects were observed in hypoxic tumors.

Conclusions:

  • Single-atom nanozymes can serve as effective catalytic ion delivery vehicles.
  • Metabolic modulation combined with targeted ion delivery offers a potent strategy to enhance cuproptosis therapy.
  • This approach shows significant potential for improving cancer treatment efficacy in challenging hypoxic tumor microenvironments.