A Self-Monitoring Single-Atom Copper Nanocapsule for Cascade-Responsive Tumor Cuproptosis Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Cuproptosis is a promising anticancer mechanism.
• Developing tumor-selective copper ion modulators is crucial for effective cuproptosis therapy.
• Existing modulators face challenges in efficiency and tumor targeting.

Purpose of the Study:

• To develop a single-atom copper-based nanocapsule (SNC) for targeted cuproptosis therapy.
• To enable cascade-responsive copper ion release within the tumor microenvironment (TME).
• To achieve synergistic cancer therapy with self-monitoring capabilities.

Main Methods:

• Constructed single-atom copper nanocapsules (SNCs) using a gold cluster/zeolite framework with Cu-imidazole/carboxyl coordination.
• Investigated TME-triggered disassembly and copper ion release via ligand protonation and competitive coordination.
• Evaluated in vitro and in vivo therapeutic efficacy and imaging performance.

Main Results:

• SNCs demonstrated controlled copper ion release in response to the TME's acidic and glutathione-rich conditions.
• Released copper ions effectively activated the cuproptosis pathway, leading to potent anticancer effects.
• The nanocapsules facilitated fluorescence recovery for real-time therapeutic monitoring.
• Achieved high-efficacy tumor therapy and imaging with no observed systemic toxicity.

Conclusions:

• The developed SNC platform offers a versatile approach for cuproptosis induction.
• This technology shows significant potential for advancing cancer therapy and biomedical imaging.
• The smart nanocapsule design addresses the need for efficient and tumor-selective copper ion delivery.