Functionalized\nIron Oxide Nanoparticles for Both Dual-Modal\nImaging and Erythropoiesis

Cancer-related\nanemia (CRA), a complication of cancer, is considered\nthe primary cause of high mortality for cancer patients. Safe and\neffective theranostics are desirable for realizing the high diagnostic\naccuracy of tumors and ameliorating CRA in the clinic. However, the\navailable theranostics do not support dual-modal imaging and the amelioration\nof CRA at the same time. In this study, we synthesized functionalized\niron oxide nanoparticles (Fe<sub>3</sub>O<sub>4</sub> NPs) modified\nwith protoporphyrin IX (PPIX) and folic acid (FA) by a one-step modification\nstrategy (Fe<sub>3</sub>O<sub>4</sub>@NH-PPIX&FA NPs) or a step-by-step\nstrategy (Fe<sub>3</sub>O<sub>4</sub>@NH-PPIX-FA NPs), aiming at both\nmagnetic resonance imaging/fluorescence imaging (MRI/FI) and erythropoiesis.\nFe<sub>3</sub>O<sub>4</sub>@NH-PPIX-FA NPs displayed better ability\nof MRI/FI than Fe<sub>3</sub>O<sub>4</sub>@NH-PPIX&FA NPs and\nhad an efficient tumor targeting of 45 min after tail vein injection\nowing to the reduction of the steric effect and extension of FA groups.\nFe<sub>3</sub>O<sub>4</sub>@NH-PPIX-FA NPs exhibited satisfactory\nerythropoiesis with up to 20% elevation of red blood cell (RBC) counts\nand hemoglobin concentrations in mice with CRA, which provided a safe\nalternative to RBC transfusions, especially for patients needing recurrent\nRBC transfusions. With excellent performance in both dual-modal imaging\nand erythropoiesis, Fe<sub>3</sub>O<sub>4</sub>@NH-PPIX-FA NPs could\nbe a powerful tool for the theranostics of cancer patients with anemia.