Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics , Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , Number 29 East Road Zhongguancun , Beijing 100190 , PR China.
University of the Chinese Academy of Sciences , Beijing 100049 , PR China.
ACS Nano. 2018 Dec 26;12(12):12721-12732. doi: 10.1021/acsnano.8b07749. Epub 2018 Dec 6.
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@ZrO nanocomposites are prepared by confining CuO nanoparticles within the cavities of mesoporous ZrO hollow nanospheres. 1-Butyl-3-methylimidazolium hexafluorophosphate (IL) is loaded to the CuO@ZrO 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@ZrO 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.
众所周知，癌细胞转移和缺氧会阻碍癌症治疗。在这项工作中，我们设计了一种基于氧化铜（CuO）在微波（MW）触发下释放氧气能力的多功能纳米复合材料，用于治疗缺氧。通过将 CuO 纳米颗粒限制在介孔 ZrO 中空纳米球的空腔内，制备了核壳结构的 CuO@ZrO 纳米复合材料。将 1-丁基-3-甲基咪唑六氟磷酸盐（IL）负载到 CuO@ZrO 纳米复合材料上，以提高微波热疗（MWTT）效果。引入 1-十四醇（PCM）来调节阿霉素（DOX）的化疗药物释放。因此，得到了 IL-DOX-PCM-CuO@ZrO 多功能（IDPC@Zr）纳米复合材料。最后，通过单甲氧基聚乙二醇巯基（mPEG-SH，5 kDa）对 IDPC@Zr 纳米复合材料进行修饰，得到 IDPC@Zr-PEG 纳米复合材料。在肿瘤治疗过程中，IDPC@Zr-PEG 纳米复合材料可在肿瘤微环境中产生氧气，从而缓解缺氧状态，提高治疗效果。体内抗肿瘤实验表明，肿瘤抑制率高达 92.14%。此外，由于 Zr 的原子序数较高，纳米复合材料的计算机断层扫描（CT）成像对比度可以增强。因此，IDPC@Zr-PEG 纳米复合材料可用于实时监测肿瘤治疗过程。这种联合治疗提供了许多机会，例如通过 MW 从 CuO 纳米颗粒中产生氧气来缓解缺氧，增强 MWTT 和化疗的联合治疗效果，以及利用 CT 成像进行潜在的治疗过程可视化，为未来肿瘤的临床治疗提供了一种很有前途的方法。
