Fe-Based Theranostic Agents Respond to the Tumor Microenvironment for MRI-Guided Ferroptosis-/Apoptosis-Inducing Anticancer Therapy

Tumor microenvironment-specific magnetic resonance imaging (MRI) contrast agents are conducive to accurate diagnoses by visualization of biochemical and pathological changes for suitable treatment. Herein, we reported a pH-responsive contrast agent DFeZd NP with MRI diagnosis and tumor treatment capabilities. DFeZd NPs can map the pH change by modulating the MR signal in different acid-base environments. Moreover, T1 signals are stronger in the tumor site, which proves efficient in distinguishing malignant tumors from normal tissues, as well as demarcating the tumor boundary. Subsequently, sustained supply of Fe through the Fe-based contrast agent leads to Fe redox cycling and lipid peroxides, inducing ferroptosis in tumor cells. Furthermore, under an acidic tumor microenvironment, in the presence of ascorbic acid, increased Fe2+ is generated, which serves as a stronger inducer of ferroptosis. Moreover, due to the different relaxivity of Fe3+ and Fe2+, redox cycling and ferroptosis in tumors can be monitored by MRI. Therefore, we propose DFeZd NPs as accessible and promising Fe-based dopamine-derived contrast agents for specific MRI imaging and ferroptosis induction for anticancer therapy.