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Updated: Jun 6, 2025

Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders
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Copper depletion-induced tumor cuproptosis.

Min Zhou1, Faheem Muhammad1,2, Yihong Zhang1

  • 1Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University Nanjing Jiangsu 210023 China weihui@nju.edu.cn.

Chemical Science
|December 2, 2024
PubMed
Summary

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This study introduces a novel nanodrug that depletes copper, inducing cancer cell death (cuproptosis) via impaired enzyme function. This copper depletion strategy offers a new avenue for tumor therapy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Copper homeostasis is vital for cell function, particularly in rapidly dividing cancer cells.
  • Cuproptosis, or copper imbalance-induced cell death, is a promising cancer treatment strategy.
  • While copper overload-induced cuproptosis is understood, copper depletion-induced cuproptosis is less explored.

Purpose of the Study:

  • To investigate copper depletion-induced cuproptosis as a novel tumor therapy.
  • To develop a smart nanodrug capable of depleting intracellular copper.
  • To elucidate the mechanism of copper depletion-induced cuproptosis.

Main Methods:

  • Developed zinc sulfide (ZnS) nanoparticles utilizing a cation exchange reaction to deplete copper.

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  • Investigated the copper-depleting efficacy and cuproptosis induction in vitro and in vivo.
  • Engineered multifunctional nanoparticles by modifying ZnS with polydopamine and a DNAzyme for enhanced tumor targeting and inhibition.

    • Main Results:

    • ZnS nanoparticles effectively depleted copper via a cation exchange reaction driven by solubility differences (ZnS/CuS).
    • Demonstrated significant tumor cuproptosis induction both in vitro and in vivo.
    • Proposed a mechanism involving copper-dependent enzyme dysfunction, distinct from copper accumulation-induced cuproptosis.
    • Developed a modified nanoconsumer exhibiting strong tumor growth and metastasis inhibition.

    Conclusions:

    • Copper depletion using ZnS nanoparticles is a viable strategy for inducing tumor cuproptosis.
    • The mechanism involves disruption of copper-containing enzymes, offering a new therapeutic approach.
    • Multifunctional nanoparticles show potential for enhanced cancer therapy by combining copper depletion with targeted delivery and inhibition.