Tumor reoxygenation for enhanced combination of radiation therapy and microwave thermal therapy using oxygen generation in situ by CuO nanosuperparticles under microwave irradiation

作者：Zengzhen Chen, Wenna Guo, Qiong Wu, Longfei Tan, Tengchuang Ma, Changhui Fu, Jie Yu, Xiangling Ren, Jianming Wang, Ping Liang, Xianwei Meng · 发表于：Theranostics · 年份：2020 · DOI：10.7150/thno.42818 · 被引用次数：46 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、Cancer, Stress, Anesthesia, and Immune Response

As known, radiation therapy (RT) can exacerbate the degree of hypoxia of tumor cells, which induces serious resistance to RT and in turn, is the greatest obstacle to RT. Reoxygenation can restore the hypoxic state of tumor cells, which plays an important role in reshaping tumor microenviroment for achieving optimal therapeutic efficacy. Herein, we report for the first time that microwave (MW)-triggered IL-Quercetin-CuO-SiO2@ZrO2-PEG nanosuperparticles (IQuCS@Zr-PEG NSPs) have been used to achieve an optimal RT therapeutic outcomes by the strategy of upregulating tumor reoxygenation, i.e. hypoxic cells acquire oxygen and return to normal state. Methods: We prepared a promising multifunctional nanosuperparticle to upregulate tumor reoxygenation by utilizing CuO nanoparticle to generate oxygen under MW irradiation in the tumor microenvironment. The IQuCS@Zr-PEG NSPs were obtained by introducing CuO nanoparticles, MW sensitizer of 1-butyl-3-methylimidazolium hexafluorophosphate (IL), radiosensitizer of Quercetin (Qu) and surface modifier of monomethoxy polyethylene glycol sulfhyl (mPEG-SH, 5k Da) into mesoporous sandwich SiO2@ZrO2 nanosuperparticles (SiO2@ZrO2 NSPs). The release oxygen by IQuCS@Zr-PEG NSPs under MW irradiation was investigated by a microcomputer dissolved oxygen-biochemical oxygen demand detector (DO-BOD) test. Finally, we used the 99m Tc-HL91 labeled reoxygenation imaging, Cellular immunofluorescence, immunohistochemistry, and TUNEL experiments to verify that th...