Development of a Supramolecular Nanocomplex Comprising Ferritin and Tannic Acid as a Ferroptosis Inducer for Cancer Therapy

Ferroptosis, triggered by the disruption of iron metabolism, is an emerging modality for cancer therapy. Excessive intracellular accumulation of iron ions induces lipid peroxidation in the plasma membrane through reactive oxygen species generated via the Fenton reaction. Ferritin, which serves as an iron ion storage protein, is also considered a potential iron source for inducing ferroptosis. We demonstrated the potential of ferritin complexed with tannic acid as a ferroptosis inducer in cancer treatment. Our system efficiently delivers ferritin to lysosomes, facilitating iron ion release via ferritin digestion, ultimately inducing ferroptotic cell death <i>in vitro</i>. Our system can induce oxidative stress even in cancer spheroids, a widely used tumor tissue model. Additionally, the complex of ferritin with tannic acid exhibited excellent therapeutic efficacy in tumor bearing mice.