MRI-Based Quantitative Evaluation of Tumor Ferroptosis Mediated by A Novel Self-Reducing Nano-Prodrug.

Abstract

Ferroptosis is triggered by iron-dependent lipid peroxidation, which shows great potential in tumor therapy. However, its biomedical applications are constrained by suboptimal therapeutic efficacy, leakage of metal ions from inducing agents, and the absence of noninvasive evaluation methods. In this study, we aimed to develop a self-reducing nano-theranostic agent (Fe@AP-SAS/RGD, FASR) for tumor-targeted ferroptosis therapy and conducted real-time magnetic resonance imaging(MRI) to monitor ferroptosis by encapsulating iron oxide particles in natural apple pectin (AP). In a weakly acidic tumor microenvironment, the strong reducing ability of AP accelerated the transformation of Fe³⁺ within FASR into highly active Fe²⁺. Subsequently, the concentration of Fe²⁺ increased and boosted the antitumor effect of ferroptosis. Notably, MRI of prostate cancer mouse models after intravenous injection of FASR NPs at varying doses revealed that the T₂ value decreased at the tumor sites and exhibited a linear correlation with the changes in ferroptosis hallmark markers, tumor weight, and volume after treatment. These findings demonstrate the capacity of T₂ mapping to quantitatively evaluate ferroptosis efficacy. This study not only introduced a tumor-targeted and self-reducing strategy to amplify ferroptosis but also pioneered a novel pathway for noninvasive imaging and monitoring of ferroptosis treatment processes within live tumors.