Copper-balancing nanoparticles combined with mild heat to enhance copper- and iron-related cell death in breast cancer treatment

T-T@Cu significantly increases mitochondrial copper accumulation in tumor cells, enhancing cuproptosis.

• Challenges in copper ion delivery and intracellular copper balance hinder effective cuproptosis in tumor cells.
• T-T@Cu utilizes a carrier-free metal-polyphenolic platform for targeted copper delivery to tumor mitochondria.
• Exposure to a 1064 nm laser with T-T@Cu leads to reduced ATP levels and down-regulates copper ion efflux proteins ATP7A/7B.
• T-T@Cu demonstrates significant glutathione depletion and responsive degradation in tumor microenvironments.
• In vitro and in vivo evaluations show strong tumor inhibition with T-T@Cu, alongside absence of significant systemic toxicity.

Simplified