Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems.

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The magnetic targeting drug delivery system is an effective way of targeting therapy. In this study, the monodisperse Fe3O4 nanoparticles with a particles size of about 180 nm were first prepared via a solvothermal method. Subsequently, the core-shell structure Fe3O4/SiO2 and Fe3O4/SiO2/polypyrrole (PPy) composite nanospheres were successfully synthesized by coating Fe3O4 nanoparticles with SiO2 shell layer using the Stöber method and PPy shell by solvothermal method in turn. The as-prepared nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), and Ultraviolet-Visible spectrophotometer (UV-Vis). The results indicated that the as-prepared composite nanospheres displayed a well-defined core-shell structure and monodispersity. The thicknesses of SiO2 shell and PPy shell were ~6 nm and ~19 nm, respectively. Additionally, the as-prepared nanoparticles exhibited high saturation magnetization of 104 emu/g, 77 emu/g, and 24 emu/g, and have great potential applications in drug delivery. The drug loading and drug release of the Fe3O4/SiO2 and Fe3O4/SiO2/PPy composite nanospheres to ibuprofen (IBU) under stirring and ultrasonication were investigated. Their drug loading efficiency and drug release efficiency under ultrasonication were all higher than 33% and 90%, respectively. The drug release analyses showed sustained release of IBU from nanospheres and followed the Korsmeyer-Peppas model.