Oxygen Production of Modified Core–Shell CuO@ZrO2 Nanocomposites by Microwave Radiation to Alleviate Cancer Hypoxia for Enhanced Chemo-Microwave Thermal Therapy

There are acknowledged risks of metastasis of cancer cells and obstructing cancer treatment from hypoxia. In this work, we design a multifunctional nanocomposite for treating hypoxia based on the oxygen release capability of CuO triggered by microwave (MW). Core-shell CuO@ZrO2 nanocomposites are prepared by confining CuO nanoparticles within the cavities of mesoporous ZrO2 hollow nanospheres. 1-Butyl-3-methylimidazolium hexafluorophosphate (IL) is loaded to the CuO@ZrO2 nanocomposites for improving microwave thermal therapy (MWTT). 1-Tetradecanol (PCM) is introduced to regulate the release of chemotherapeutic drugs of doxorubicin (DOX). Thus, the IL-DOX-PCM-CuO@ZrO2 multifunctional (IDPC@Zr) nanocomposites are obtained. Finally, IDPC@Zr nanocomposites are modified by monomethoxy polyethylene glycol sulfhydryl (mPEG-SH, 5 kDa) (IDPC@Zr-PEG nanocomposites). IDPC@Zr-PEG nanocomposites can produce oxygen in the tumor microenvironment during the course of tumor treatment, thereby alleviating the hypoxic state and improving the therapeutic effect. In vivo antitumor experiments demonstrate a very high tumor inhibition rate of 92.14%. In addition, computed tomography (CT) imaging contrast of the nanocomposites can be enhanced due to the high atomic number of Zr. Therefore, IDPC@Zr-PEG nanocomposites can be applied for monitoring the tumor-treatment process in real time. This combined therapy offers many opportunities, such as the production of oxygen from CuO nanoparticles by MW to alleviate hypoxia, the enhancement of combined treatment of MWTT and chemotherapy, and the potential application of CT imaging to visualize the treatment process, which therefore provides a promising method for the clinical treatment of tumors in the future.