Photothermal nanozyme-ignited Fenton reaction-independent ferroptosis for breast cancer therapy.

Ferroptosis is a type of programmed cell death caused by the iron-dependent lipid hydroperoxide pathway and has attracted significant interest. However, Fenton reaction-dependent ferroptosis has shown unsatisfactory therapeutic effects in tumor therapy, mainly due to inadequate reaction conditions in the tumor microenvironment. Here, we report a new strategy for Fenton-independent pathway by employing photothermal nanozyme to overcome limitations of the low efficiency of Fenton reaction. Specifically, we used iron redox pair (Fe2+/Fe3+)-containing hollow mesoporous Prussian blue (HMPB) nanocubes as the iron sources to fabricate iron-loaded liposome (HMPB@Lip). HMPB@Lip not only exerts the photothermal therapy, but also functions as nanozyme catalyzing lipid peroxidation for ferroptosis therapy. Importantly, Fenton reaction-independent ferroptosis triggered by photothermal nanozyme achieved effective tumor ablation. Therefore, HMPB@Lip can be used as a potential multifunctional nanozyme for effective Fenton reaction-independent ferroptosis therapy.