Oxygen-enriched Fe3O4/Gd2O3 nanopeanuts for tumor-targeting MRI and ROS-triggered dual-modal cancer therapy through platinum (IV) prodrugs delivery

In this study, we designed a novel peanut probe that could load oxygen molecules and platinum(IV) prodrug (GINP-Pt) to elicit ferroptosis and apoptosis in cancer cells. In addition, transferrin-labeled amino polyethylene glycol (Tf-PEG-NH2) was equipped to GINP-Pt to obtain targeting and pH-responsive ability. When the system enters cancer cells, platinum(IV) can be released and reduced to platinum(II) by depleting glutathione (GSH), resulting in a ROS increase. Meanwhile, Tf-PGINP-Pt deliver abundant oxgen molecules into cancer cells, significantly elevating oxygen levels. Moreover, generated platinum(II) can activate nicotinamide adenine dinucleotide phosphate oxidases (NOXs), accelerating the conversion of oxygen to superoxide anions and enhancing downstream H2O2 levels. Next, Fe2+/Fe3+ ions released from Tf-PGINP-Pt rapidly converted H2O2 into highly toxic OH, causing DNA and mitochondrial membrane damage, resulting in cell ferroptosis. Notably, platinum(II) can coordinate with DNA bases and form Pt-DNA adducts, inhibiting DNA replication and inducing cell apoptosis. In addition, the contrast superimposed effect originated from Gd2O3 and Fe3O4 in Tf-PGINP-Pt endows accurate diagnostic capability for tumor identification, achieving MRI-guided dual-modal cancer therapy. Therefore, this work provides an unique and clinically promising strategy for accurate diagnosis and effective therapy of cancer.