Polypeptide-Folded Artificial Ferroprotein Promotes Ferroptosis in Multiple Tumor Cells

Area of Science:

• Biomaterials Science
• Nanotechnology
• Biochemistry

Background:

• Current nanozymes lack the organic framework and flexibility of natural enzymes.
• Mimicking metalloproteins via polypeptide folding offers a more similar approach.

Purpose of the Study:

• To synthesize and characterize a novel artificial ferroprotein (AFP) with iron nanoclusters.
• To evaluate the AFP's potential in inducing cancer cell death (ferroptosis).

Main Methods:

• Synthesis of a triblock PEG-polypeptide copolymer using NCA polymerization.
• Intramolecular cross-linking of alkyne side groups with Fe3(CO)12 coordination.
• Thermolysis to remove CO ligands and form Fe/FeO nanoclusters within the polypeptide.

Main Results:

• The synthesized triblock copolypeptide showed no cytotoxicity to normal human cell lines.
• The resulting AFPs induced significant ferroptosis in multiple cancer cell lines (PANC-1, HT1080, MCF-7, A549).
• Effective ferroptosis induction was observed even at a low iron content of 1.6 wt %.

Conclusions:

• Artificial ferroproteins offer a promising alternative to traditional nanozymes.
• AFPs demonstrate potential as targeted cancer therapeutics by inducing ferroptosis.
• The design overcomes limitations of current nanozymes by incorporating a degradable organic framework and flexible structure.