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

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 250µgmL^-1 for 48h. Thus, our results revealed that the Fe₃O₄@SiO₂-DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy.