Modified core-shell magnetic mesoporous zirconia nanoparticles formed through a facile outside-to-inside way for CT/MRI dual-modal imaging and magnetic targeting cancer chemotherapy

Iron oxide based magnetic nanoparticles (MNPs) as typical theranostic nanoagents have been popularly used in various biomedical applications. Conventional core-shell MNPs are usually synthesized from inside to outside. This method has strict requirements on the interface properties of magnetic cores and the precursors of the coating shell. The shape and size of MNPs are significantly influenced by that of the pre-synthesized magnetic cores. Most core-shell MNPs have only single T2W MRI imaging ability. Herein, we propose a new synthetic strategy for core-mesoporous shell structural MNPs, where hollow mesoporous nanospheres which exhibit an intrinsic property for both CT imaging and drug loading were used as the shell and the magnetic cores were produced in the cavity of the shell. A new type of MNPs, Fe3O4@ZrO2 nanoparticles (M-MZNs), were developed using this facile outside-to-inside way, where multiple Fe3O4 nanoparticles grew inside the cavity of the mesoporous hollow ZrO2 nanospheres through chemical coprecipitation. The obtained MNPs not only exhibited superior magnetic properties and CT/MR imaging ability but also high drug loading capacity. In vitro experiment results revealed that M-MZNs-PEG loaded with doxorubicin (DOX) presented selective growth inhibition against cancer cells due to pH-sensitive DOX release and enhanced endocytosis by cancer cells under a magnetic field. Furthermore, the proposed MNPs exhibited CT/MRI dual modal imaging ability and effective physical targeting to tumor sites in vivo. More importantly, experiments of magnetic targeting chemotherapy on tumor bearing mice demonstrated that the nanocomposites significantly suppressed tumor growth without obvious pathological damage to major organs. Henceforth, this study provides a new strategy for CT/MRI dual-modal imaging guided and magnetic targeting cancer therapy.