FeP‐Based Nanotheranostic Platform for Enhanced Phototherapy/Ferroptosis/Chemodynamic Therapy

Abstract Ferroptosis is an iron‐dependent and lipid peroxides (LPO)‐overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near‐infrared photo‐responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near‐infrared (NIR‐808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2‐weighted magnetic resonance imaging (MRI) property. In summary, the FeP‐based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.