Copper-Induced Supramolecular Peptide Assemblies for Multi-Pathway Cell Death and Tumor Inhibition.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Supramolecular Chemistry

Background:

• Self-assembly is key for biomaterial fabrication, but controlling morphology and function is challenging.
• Copper peptides in plasma inspire new biomaterial designs.
• Precise control over self-assembled nanostructures is crucial for advanced applications.

Purpose of the Study:

• To design a synthetic precursor, FcGH, capable of self-assembly via distinct pathways.
• To investigate the role of Cu2+ in directing FcGH self-assembly and its impact on morphology.
• To evaluate the therapeutic potential of Cu2+-induced nanodrugs for synergistic cancer treatment.

Main Methods:

• Designed synthetic precursor FcGH for self-assembly.
• Utilized spontaneous and Cu2+-induced self-assembly pathways.
• Adjusted Cu2+ concentration to tune assembly morphology.
• Co-assembled FcGH with 10-hydroxycamptothecin (HCPT) for nanodrug development.

Main Results:

• FcGH self-assembled into tunable morphologies (nanoparticles, fibers) based on Cu2+ concentration.
• Cu2+-induced nanoparticles showed higher cellular uptake than spontaneous fibers.
• Cu2+-induced assembly occurred efficiently at a 1:1 Cu2+ to FcGH molar ratio.
• Co-assembled nanodrugs enhanced cancer cell death and immunogenicity compared to free HCPT.

Conclusions:

• Cu2+-induced self-assembly offers precise control over nanostructure morphology and function.
• This method provides an efficient route for developing nanodrugs with improved therapeutic outcomes.
• Cu2+-induced nanodrugs demonstrate potential for synergistic tumor therapy by enhancing cell death and immunogenicity.