A PROTAC-Based Cuproptosis Sensitizer in Lung Cancer Therapy

© 2025 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 37(2025), 34 vom: 13. Aug., Seite e2501435
1. Verfasser: Wang, Yu (VerfasserIn)
Weitere Verfasser: Yao, Xiaoyang, Lu, Yingying, Ruan, Juan, Yang, Zhao, Wang, Chunhui, Yang, Niantong, Gao, Yan, Shi, Shuo
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2025
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article PROTAC apoptosis cuproptosis glutathione glycolysis Copper 789U1901C5 Proteolysis Targeting Chimera Glutathione mehr... GAN16C9B8O Sulfides Tumor Suppressor Protein p53 Nanoparticle Drug Delivery System Reactive Oxygen Species Fenton's reagent Hydrogen Peroxide BBX060AN9V Iron E1UOL152H7
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520 |a As an autonomous form of regulated cell death, cuproptosis depends on copper (Cu) and mitochondrial metabolism. However, the principle metabolic pathway known as glycolysis (Warburg effect) and high glutathione (GSH) levels of tumor cells inevitably lead to suboptimal efficacy in cuproptosis. Hence, depleting the endogenous GSH within tumors and shifting from glycolysis to mitochondrial respiration are crucial factors for augmenting cuproptosis. In this study, a proteolysis targeting chimera (PROTAC)-based cuproptosis sensitizer (CuS-MDCS) is innovatively constructed, which not only can induce cuproptosis and reactive oxygen species production via copper ions but also can regulate the expression of p53 protein via PROTACs through the ubiquitin-proteasome system in tumor cells, thus achieving endogenous GSH depletion and a shift from glycolysis to mitochondrial respiration, making cancer cells more sensitive to cuproptosis. Importantly, in vitro and in vivo experiments have verified that CuS-MD@CS effectively targets A549 cells and suppresses tumor growth through cuproptosis and apoptosis, exhibiting promising therapeutic responses. The novel PROTAC-based cuproptosis sensitizer CuS-MD@CS provides a new strategy for sensitizing cuproptosis and offers new hope for effective lung cancer treatment 
650 4 |a Journal Article 
650 4 |a PROTAC 
650 4 |a apoptosis 
650 4 |a cuproptosis 
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650 4 |a glycolysis 
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650 7 |a 789U1901C5  |2 NLM 
650 7 |a Proteolysis Targeting Chimera  |2 NLM 
650 7 |a Glutathione  |2 NLM 
650 7 |a GAN16C9B8O  |2 NLM 
650 7 |a Sulfides  |2 NLM 
650 7 |a Tumor Suppressor Protein p53  |2 NLM 
650 7 |a Nanoparticle Drug Delivery System  |2 NLM 
650 7 |a Reactive Oxygen Species  |2 NLM 
650 7 |a Fenton's reagent  |2 NLM 
650 7 |a Hydrogen Peroxide  |2 NLM 
650 7 |a BBX060AN9V  |2 NLM 
650 7 |a Iron  |2 NLM 
650 7 |a E1UOL152H7  |2 NLM 
700 1 |a Yao, Xiaoyang  |e verfasserin  |4 aut 
700 1 |a Lu, Yingying  |e verfasserin  |4 aut 
700 1 |a Ruan, Juan  |e verfasserin  |4 aut 
700 1 |a Yang, Zhao  |e verfasserin  |4 aut 
700 1 |a Wang, Chunhui  |e verfasserin  |4 aut 
700 1 |a Yang, Niantong  |e verfasserin  |4 aut 
700 1 |a Gao, Yan  |e verfasserin  |4 aut 
700 1 |a Shi, Shuo  |e verfasserin  |4 aut 
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773 1 8 |g volume:37  |g year:2025  |g number:34  |g day:13  |g month:08  |g pages:e2501435 
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