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

• Oxygen-enriched Fe 2 O 3 /Gd 2 O 3 nanopeanut theranostic system (Tf-PGINP-Pt) was developed. • Tf-PGINP-Pt deliver oxygen molecules to cancer cells, enhancing oxygen levels. • Nanopeanut enhanced ROS and inactivated GPX4 in cancer cells, leading to ferroptosis. • Pt(IV) in Tf-PGINP-Pt was reduced to Pt(II) by depleting GSH, accelerating apoptosis. • Contrast superimposed effect of Tf-PGINP-Pt endowed highly efficient MRI capability. 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-NH 2) 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 H 2 O 2 levels. Next, Fe2+/Fe3+ ions released from Tf-PGINP-Pt rapidly converted H 2 O 2 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 Gd 2 O 3 and Fe 3 O 4 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. [ABSTRACT FROM AUTHOR]