Abstract

The treatment of lung cancer remains a significant clinical challenge. Inducing ferroptosis is a promising therapeutic strategy to overcome treatment resistance in lung cancer. Herein, we report a composite nanozyme, Fe@Arc, engineered by coordinating arctigenin with iron ions followed by a high-temperature carbonization. This fabrication method yielded a nanozyme with a high drug-loading capacity and controlled release kinetics. Following intravenous administration, Fe@Arc efficiently accumulated at the tumor site owing to its enhanced permeability and retention effect. In the tumor site, it exerted a potent anti-tumor effect by catalyzing the Fenton reaction and releasing arctigenin, which synergistically triggered ferroptosis in cancer cells. This work presents a multifaceted platform that not only overcomes the pharmacological limitations of herbal extracts but also establishes a robust framework for developing novel ferroptosis inducers, demonstrating significant potential for clinical translation.