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Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders
Published on: April 28, 2023
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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
Summary
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.
- 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.

