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介孔过氧化钛中软X射线增强活性氧生成及其在肿瘤协同治疗中的应用

Soft X-ray-Enhanced Reactive Oxygen Species Generation in Mesoporous Titanium Peroxide and the Application in Tumor Synergistic Therapy.

作者信息

Dai Zideng, Cao Junkai, Guo Zhaoming, Zheng Kun, Song Xue-Zhi, Wen Wen, Xu Xinyu, Qi Xiuyu, Ohara Satoshi, Tan Zhenquan

机构信息

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China.

School of Chemical Engineering, Dalian University of Technology, Panjin, Liaoning 124221, China.

出版信息

ACS Appl Bio Mater. 2020 Nov 16;3(11):7408-7417. doi: 10.1021/acsabm.0c00538. Epub 2020 Oct 26.

Abstract

Mesoporous titanium peroxide TiO nanospheres with a high surface area are synthesized for the application of an advanced drug system. The mesoporous TiO nanospheres have a high specific surface area of 681.89 m/g and suitable pore size (∼3 nm) that can effectively upload doxorubicin (DOX) and possesses a high drug storage capacity of 146.08%. They show a distinct ability to produce reactive oxygen species (ROS) in response to X-ray irradiation, which can effectively improve the radiotherapy in tumor treatment using the lung cancer cell line. The ROS generation of TiO is more than ten-fold higher than that of TiO. No apparent toxicity is found for the TiO material itself without X-ray irradiation. In vitro and in vivo experiments show that TiO/DOX nanodrugs significantly enhance cytotoxicity in response to X-ray irradiation. CCK8 assays display that the TiO/DOX nanodrug has higher cancer treatment efficiency in response to X-ray irradiation because of the synergistic effect of chemotherapy and generation of ROS. In the in vivo experiments using lung cancer tumor-bearing mice model, the tumor inhibition rate in the TiO/DOX + X-ray group increased by 90.4% compared to the untreated control group, showing a good synergistic chemo-radiotherapy effect in tumor treatment.

摘要

合成了具有高比表面积的介孔过氧化钛TiO纳米球,用于先进药物系统的应用。介孔TiO纳米球具有681.89 m²/g的高比表面积和合适的孔径(约3 nm),能够有效负载阿霉素(DOX),且药物储存容量高达146.08%。它们在X射线照射下表现出明显的产生活性氧(ROS)的能力,这可以有效改善使用肺癌细胞系进行肿瘤治疗中的放射治疗效果。TiO产生的ROS比TiO高出十多倍。在没有X射线照射的情况下,TiO材料本身未发现明显毒性。体外和体内实验表明,TiO/DOX纳米药物在X射线照射下显著增强细胞毒性。CCK8检测显示,由于化疗和ROS产生的协同作用,TiO/DOX纳米药物在X射线照射下具有更高的癌症治疗效率。在使用肺癌荷瘤小鼠模型的体内实验中,与未治疗的对照组相比,TiO/DOX + X射线组的肿瘤抑制率提高了90.4%,在肿瘤治疗中显示出良好的协同放化疗效果。

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