Tumor microenvironment triggered iron-based metal organic frameworks for magnetic resonance imaging and photodynamic-enhanced ferroptosis therapy

Photodynamic therapy (PDT) primarily relies on the generation of reactive oxygen species (ROS) to eliminate tumor cells. However, the elevated levels of glutathione (GSH) within tumor cells can limit the efficacy of PDT, posing a challenge to achieve complete tumor eradication. Herein, a porous iron-based metal–organic frameworks (PEG-Fe-MOFs) nanoplatform was developed for the combined application of PDT and ferroptosis in cancer treatment. The coordination between tetrakis (4-carboxyphenyl) porphyrin (TCPP) and ferric (Fe 3+ ) enabled PEG-modified Fe-MOFs (PEG-Fe-MOFs) to deliver excellent T 1 -weighted magnetic resonance (MR) imaging performance in physiological environments. Within the tumor microenvironment (TME), PEG-Fe-MOFs gradually degraded to release TCPP, which could be utilized for fluorescence imaging. Moreover, Fe 2+ enhanced intracellular ROS levels via the Fenton reaction, generating hydroxyl radicals that further amplified ROS production. This synergistic effect comprising increased ROS levels and GSH depletion augmented the efficacy of PDT while simultaneously inducing robust ferroptosis in tumor cells, thereby maximizing therapeutic outcomes. Both in vitro and in vivo experiments have demonstrated the superior T 1 weighted MR and fluorescence imaging capabilities of PEG-Fe-MOFs, along with its potent synergistic therapeutic effects on tumors. These results highlighted the potential of this nanoplatform for combining PDT and ferroptosis in cancer treatment.