Microwave (MW) therapy, as a promising type of thermal therapy, has been attracting more and more attention from scientists. The combination of thermal and chemotherapy is of great significance in the latest studies of synergistic tumor therapy. However, the research on the MW therapy mechanism, especially the nonthermal effect applied in the combined cancer therapy, is not thorough enough. Pleasantly, we have discovered that nonthermal MW irradiation can promote the cellular uptake of nanoparticles and anticancer drugs via experiments in vitro and in vivo. Therefore, multifunctional nanoplatforms have been designed for enhanced tumor inhibition by loading ionic liquids (ILs), doxorubicin hydrochloride (DOX), and phase change materials (PCMs) into ZrO hollow nanoparticles. PCMs act as MW switches. The as-made IL-DOX-PCM@ZrO nanoplatforms were injected into H22-tumor-bearing mice via the tail vein. Mild microwave irradiation (0.9 W, 450 MHz) was then applied. The thermal effect of MW could cause the temperature of the tumor site to rise (58 °C). On the other hand, it will trigger the MW switch to open and release DOX when the temperature is high enough. At the same time as drug release, a MW nonthermal effect could improve the cellular uptake of nanomaterials and anticancer drugs. The multisynergistic effect can promote the survival rate of the IL-DOX-PCM@ZrO+MW group to 100%. The results of the tumor therapy experiment in vivo demonstrated that as-made multifunctional IL-DOX-PCM@ZrO nanoplatforms could enhance the therapeutic outcome of combined thermal and chemotherapy under mild MW irradiation.

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This paper develops a simple multifunctional theranostic platform using an IL@ZrO2 nanostructure for CT imaging guided tumor microwave thermotherapy.