Nanofibers made of copper-binding peptides disrupt cancer cells

While toxic in high concentrations, copper is essential to life as a trace element. Many tumors require significantly more copper than healthy cells for growth – a possible new point of attack for cancer treatment.

Research team from the Max Planck Institute for Polymer Research has now introduced a novel method by which copper is effectively removed from tumor cells, killing them.

At the heart of their system are the copper-binding domains of the chaperone Atox1. The team attached a component to this peptide that promotes its uptake into tumor cells. An additional component ensures that the individual peptide molecules aggregate into nanofibers once they are inside the tumor cells. In this form, the fiber surfaces have many copper-binding sites in the right spatial orientation to be able to grasp copper ions from three sides with thiol groups (chelate complex).

The affinity of these nanofibers for copper is so high that they also grab onto copper ions in the presence of copper-binding biomolecules. This drains the copper pools in the cells and deactivates the biomolecules that require copper. As a consequence, the redox equilibrium of the tumor cell is disturbed, leading to an increase in oxidative stress, which kills the tumor cell.

In experiments carried out on cell cultures under special conditions, more than 85% of a breast cancer cell culture died off after 72 hours while no cytotoxicity was observed for a healthy cell culture.

Image source: Jeena et al. (2024), Angewandte Chemie International Edition.