A multi-controlled drug delivery system based on magnetic mesoporous Fe₃O₄ nanopaticles and a phase change material for cancer thermo-chemotherapy

Herein a novel multi-controlled drug release system for doxorubicin (DOX) was developed, in which monodisperse mesoporous Fe₃O₄ nanoparticles were combined with a phase change material (PCM) and polyethylene glycol 2000 (PEG2000). It is found that the PCM/PEG/DOX mixture containing 20% PEG could be dissolved into water at 42 °C. The mesoporous Fe₃O₄ nanoparticles prepared by the solvothermal method had sizes of around 25 nm and exhibited a mesoporous microstructure. A simple solvent evaporation process was employed to load the PCM/PEG/DOX mixture on the mesoporous Fe₃O₄ nanoparticles completely. In the Fe₃O₄@PCM/PEG/DOX system, the pores of the Fe₃O₄ nanoparticles were observed to be filled with the mixture of PCM/PEG/DOX. The Fe₃O₄@PCM/PEG/DOX system showed a saturation magnetization value of 50.0 emu g⁻¹, lower than 71.1 emu g⁻¹ of the mesoporous Fe₃O₄ nanoparticles, but it was still high enough for magnetic targeting and hyperthermia application. The evaluation on drug release performance indicated that the Fe₃O₄@PCM/PEG/DOX system achieved nearly zero release of DOX in vitro in body temperature, while around 80% of DOX could be released within 1.5 h at the therapeutic threshold of 42 °C or under the NIR laser irradiation for about 4 h. And a very rapid release of DOX was achieved by this system when applying an alternating magnetic field. By comparing the systems with and without PEG2000, it is revealed that the presence of PEG2000 makes DOX easy to be released from 1-tetradecanol to water, owing to its functions of increasing the solubility of DOX in 1-tetradecanol as well as decreasing the surface tension between water and 1-tetradecanol. The novel drug release system shows great potential for the development of thermo-chemotherapy of cancer treatment. (paper)