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ACS Nano

ACS Nano

IF: 15.8
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A Peptide-Copper Self-Assembled Nanoparticle for Enhanced Cuproptosis by Metabolic Reprogramming in Tumor Cells

Published:3 December 2024 DOI: 10.1021/acsnano.4c12123
Wei Zhang, Ziling Chen, Chen Xiong, Lizhen Yuan, Jing-Jing Hu, Jun Dai, Fan Xia, Xiaoding Lou

Abstract

Cuproptosis is a type of metabolic cell death and exhibits great potential for cancer treatment. However, currently, most cuproptosis-based therapies are primarily effective in tumor cells reliant on mitochondrial respiration, limiting their broader application. The Warburg effect highlights that many tumors predominantly rely on glycolysis to meet their rapid metabolic demands, but glycolysis-dependent cells are less sensitive to copper ions than their mitochondrial-respiration-dependent counterparts, making it difficult to induce cuproptosis in these cells. Herein, we designed a copper-loaded peptide-based nanoparticle (MHRC@Cu) to enhance cuproptosis by metabolic reprogramming in a wider range of glycolysis-dependent tumor cells. Specifically, triggered by the acidic environment and laser irradiation, MHRC@Cu effectively released Cu2+ inside the cells. Then the peptide-conjugated probe (MHRC) reprogrammed glycolysis-dependent tumor cells, making them more dependent on mitochondrial respiration and increasing their sensitivity to copper ions. Additionally, the H2O2 generated by the photodynamic effect underwent Fenton reaction with Cu2+ in situ, producing highly toxic ·OH, which depleted GSH and disrupted copper efflux protein, thereby exacerbating copper deposition in cells. Through these synergistic mechanisms, MHRC@Cu significantly enhanced cuproptosis in glycolysis-dependent tumor cells, achieving up to 96% inhibition of tumor growth. This copper-loaded peptide-based nanoparticle offers a versatile and potent strategy for enhancing cuproptosis and may inspire the development of advanced self-assembled nanotherapeutic platforms.

Substances (5)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Sodium ascorbate 134-03-2 C6H7NaO6 636 suppliers $5.00-$1164.80
Propidium iodide 25535-16-4 C27H34IN4+ 328 suppliers $29.00-$1780.00
4-methylquinoline 491-35-0 C10H9N 284 suppliers $10.00-$1057.50
1,4-Diiodobutane 628-21-7 C4H8I2 241 suppliers $6.00-$2465.93
JC-1 3520-43-2 C25H27Cl4N4.I 118 suppliers $68.00-$3900.00

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