Functionalized Iron Oxide Nanoparticles for Both Dual-Modal Imaging and Erythropoiesis

Cancer-related anemia (CRA), a complication of cancer, is considered the primary cause of high mortality for cancer patients. Safe and effective theranostics are desirable for realizing the high diagnostic accuracy of tumors and ameliorating CRA in the clinic. However, the available theranostics do not support dual-modal imaging and the amelioration of CRA at the same time. In this study, we synthesized functionalized iron oxide nanoparticles (Fe₃O₄ NPs) modified with protoporphyrin IX (PPIX) and folic acid (FA) by a one-step modification strategy (Fe₃O₄@NH-PPIX&FA NPs) or a step-by-step strategy (Fe₃O₄@NH-PPIX-FA NPs), aiming at both magnetic resonance imaging/fluorescence imaging (MRI/FI) and erythropoiesis. Fe₃O₄@NH-PPIX-FA NPs displayed better ability of MRI/FI than Fe₃O₄@NH-PPIX&FA NPs and had an efficient tumor targeting of 45 min after tail vein injection owing to the reduction of the steric effect and extension of FA groups. Fe₃O₄@NH-PPIX-FA NPs exhibited satisfactory erythropoiesis with up to 20% elevation of red blood cell (RBC) counts and hemoglobin concentrations in mice with CRA, which provided a safe alternative to RBC transfusions, especially for patients needing recurrent RBC transfusions. With excellent performance in both dual-modal imaging and erythropoiesis, Fe₃O₄@NH-PPIX-FA NPs could be a powerful tool for the theranostics of cancer patients with anemia.