This work demonstrates a simple and feasible method to construct magnetic and luminescence nanospheres for drug delivery. Fe3O4@SiO2 core-shell structure nanospheres were firstly prepared, the matrix films capable of loading and release of anionic molecules were then successfully deposited on the surface of the Fe3O4@SiO2 nanospheres via a layer-by-layer (LbL) assembly method by using luminescence microgels (named FITC-PAHD) and chondroitin sulfate (CS) as building blocks and verified by ultraviolet visible and photoluminescence measurements, transmission electron microscopy and fluorescence microscopy. The model drug ibuprofen was loaded into the Fe3O4@SiO2@(FITC-PAHD/CS)(4) nanospheres because of the electrostatic interaction of ibuprofen with amine groups in the FITC-PAHD microgels via ion exchange. Ibuprofen loaded in the nanospheres can be released in 0.9% normal saline in a sustainable way for 12 days and the Fe3O4@SiO2@(FITC-PAHD/CS)(4) nanospheres have a maximum uptake amount of ibuprofen of 117 mg.g(-1). The magnetic and luminescence nanospheres with high loading capacity are expected to be widely useful as carriers for drug delivery followed by magnetic separation and luminescent detection. (C) 2012 Elsevier B.V. All rights reserved.