Rationale: Ferroptosis is a regulated process of cell death caused by iron-dependent accumulation of lipid hydroperoxides (LPO). It is sensitive to epithelial-to-mesenchymal transition (EMT) cells, a well-known therapy-resistant state of cancer. Previous studies on nanomaterials did not investigate the immense value of ferroptosis therapy (FT) in epithelial cell carcinoma during EMT. Herein, we describe an EMT-specific nanodevice for a comprehensive FT strategy involving LPO burst.

Photodynamic therapy relies on photosensitizers to generate cytotoxic reactive oxygen species (ROS) resulting in the apoptois of tumor cells. However, there is an antioxidant system that impedes the elevation of oxidation levels in tumor cells. Thus, photodynamic therapy may exhibit insufficient curative effects due to ungenerous reactive oxygen species levels. Herein, we describe tumor-specific activated photodynamic therapy using an oxidation-regulating strategy.