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Cascade-targeting copper homeostasis nano-regulators for mild-photothermal boosted cuproptosis/ferroptosis mediated breast cancer therapy
Copper-balancing nanoparticles combined with mild heat to enhance copper- and iron-related cell death in breast cancer treatment
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Abstract
T-T@Cu significantly increases mitochondrial copper accumulation in tumor cells, enhancing .
- 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.
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Key numbers
100%
Tumor Inhibition Rate
Observed in 4T1 breast cancer models treated with T-T@Cu.
5.4-fold
Copper Ion Concentration Increase
Measured in 4T1 cells treated with T-T@Cu and mild photothermal irradiation.