Template-etching route to construct uniform rattle-type Fe3O4@SiO2 hollow microspheres as drug carrier

- Template-etching route was developed to synthesize rattle-type Fe3O4@SiO2 hollow microspheres.
- The parameters of rattle-type Fe3O4@SiO2 hollow microspheres including silica shell and void volume could be controlled.
- The rattle-type Fe3O4@SiO2 hollow microspheres exhibited shell-thickness-dependent and pH responsive drug release features.

Template-etching strategy was put forward to synthesize rattle-type magnetic silica (Fe3O4@SiO2) hollow microspheres in a controlled way. During the experiment, monodisperse Fe2O3 microspheres were fabricated as physical template to generate uniform Fe2O3@SiO2 with controlled shell thicknesses through sol-gel method, and the subsequent Fe2O3 template etching process created variable space between Fe2O3 core and SiO2 shell, and the final calcination process transformed rattle-type Fe2O3@SiO2 hollow microspheres into corresponding Fe3O4@SiO2 product in hydrogen/nitrogen atmosphere. Compared with traditional physical template, here template-etching synthesis of rattle-type hollow microspheres saved the insertion of middle shells and their removal, which simplified the synthesis process with controllable core size and shell thickness. The rattle-type Fe3O4@SiO2 hollow microspheres as drug carrier show efficient doxorubicin (DOX) loading, and the release rate of DOX loaded the rattle-type Fe3O4@SiO2 hollow microspheres exhibit a surprising shell-thickness-dependent and a pH responsive drug release features. Additionally, MTT assays in HeLa cells demonstrated that the Fe3O4@SiO2 nanocarriers were non-toxic even at the concentration of 250 µg mL− 1 for 48 h. Thus, our results revealed that the Fe3O4@SiO2-DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy.