Gastric cancer peritoneal metastasis (PM) is driven by a protective tumor microenvironment (TME), with cancer-associated fibroblasts (CAFs) contributing to therapy resistance via high GPX4 levels that prevent ferroptosis. To overcome this barrier, researchers developed a multifunctional theranostic nanoplatform, CDDP2@MSPION@GP3/FAPI. This system combines iron oxide nanoparticles (MSPION) that release Fe²⁺/Fe³⁺ in the acidic TME to trigger lipid peroxidation, cisplatin (CDDP) to disrupt antioxidant defenses and inactivate GPX4, and FAPI, a fibroblast activation protein inhibitor, to selectively target CAFs. Gd-PASP (GP) enables T1-weighted MRI for real-time imaging.
The platform enhances uptake in CAFs through FAPI targeting, inducing dual-cell ferroptosis in both cancer cells and CAFs, evidenced by increased ROS and lipid peroxides. Its pH-responsive T2-to-T1 MRI signal produces a “light-up” effect, allowing high-contrast visualization of the acidic TME.
By simultaneously targeting tumor and stromal cells, this strategy integrates precise therapy with noninvasive imaging, offering a promising theranostic approach for gastric cancer PM.