From ROS to Cuproptosis: The molecular evolution of copper nanotherapeutics

Area of Science:

• Biomedical Nanotechnology
• Materials Science
• Molecular Toxicology

Background:

• Copper-based nanomaterials are gaining traction for biomedical uses.
• Nanotechnology advances enable multifunctional nanoplatforms for targeted intervention and theranostics.
• Copper nanostructures' bioactivity depends on complex factors like size, morphology, and aggregation.

Purpose of the Study:

• To systematically assess the developmental trajectory of copper-containing nanostructures.
• To explore novel copper-related cell death pathways (cuproptosis and ferroptosis) for therapeutic potential.
• To evaluate bimetallic Cu/Se nanoparticles as a promising theranostic platform.

Main Methods:

• Review of literature on copper nanostructures, including single-component, anisotropic, composite, and bimetallic forms.
• Analysis of molecular toxicology studies identifying cuproptosis and ferroptosis mechanisms.
• Assessment of Cu/Se nanoparticles' properties, including redox balance and photothermal efficiency.

Main Results:

• Bimetallic Cu/Se nanoparticles reconcile copper's pro-oxidant activity with selenium's antioxidant and photothermal properties.
• Cuproptosis and ferroptosis pathways offer new avenues for selective cancer therapy.
• Anisotropic nanostructures show potential for multimodal imaging and combined therapy, but face challenges in reproducibility and clearance.

Conclusions:

• Copper nanoplatforms, particularly bimetallic Cu/Se systems, exhibit significant potential for theranostic applications.
• Understanding cuproptosis and HIF-1α modulation is key to developing targeted copper-based therapies.
• Future research must focus on "clearance-by-design," green synthesis, and comprehensive in vivo studies for clinical translation.