Dai Zideng, Xu Xinyu, Guo Zhaoming, Zheng Kun, Song Xue-Zhi, Qi Xiuyu, Tan Zhenquan
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China; School of Chemical Engineering, Dalian University of Technology, Panjin 124221, China.
School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111666. doi: 10.1016/j.msec.2020.111666. Epub 2020 Oct 22.
Ultra-thin two-dimensional nanosheets have attracted increasing attention due to their great application prospects in nanomaterial science and biomedicine. Herein, we report the preparation of exfoliated raw and oxidized 4-layer TiO (O-TiO) and their ability to produce reactive oxygen species (ROS). The results show that O-TiO nanosheets can effectively produce ROS induced by X-ray irradiation. The 4-layer nanosheets can quickly load doxorubicin (DOX) within 5 min with a high loading rate to obtain a novel nanodrug system through their electrostatic adsorption capacity, and they exhibit a sustained release behavior. In this way, chemotherapy, radiation therapy and photodynamic therapy effectively combine for cancer synergistic treatment. We evaluated the cytotoxicity, cellular uptake and intracellular location of the O-TiO nanosheet-based drug delivery system in A549 lung cancer cells. Our results show that the O-TiO/DOX complex is more cytotoxic to A549 cells than free DOX since a low concentration of loaded DOX (10 μg/mL) with a low dose of X-rays can cause the complete apoptosis of tumor cells. This work reveals that the therapeutic effect of DOX-loaded O-TiO nanosheets is strongly dependent on their loading mode, and the effects of chemotherapy and photodynamic therapy are enhanced under X-ray irradiation, which allows O-TiO nanosheet use as a photo-activated drug carrier. This work provides a new strategy for preparing 2D metal oxide nanosheets toward biomedical applications.
超薄二维纳米片因其在纳米材料科学和生物医学领域的巨大应用前景而受到越来越多的关注。在此，我们报告了剥离的原始和氧化的4层TiO（O-TiO）的制备及其产生活性氧（ROS）的能力。结果表明，O-TiO纳米片能有效产生由X射线照射诱导的ROS。4层纳米片可通过其静电吸附能力在5分钟内快速负载阿霉素（DOX），负载率高，从而获得一种新型纳米药物系统，并且它们表现出缓释行为。通过这种方式，化疗、放疗和光动力疗法有效地结合用于癌症协同治疗。我们评估了基于O-TiO纳米片的药物递送系统在A549肺癌细胞中的细胞毒性、细胞摄取和细胞内定位。我们的结果表明，O-TiO/DOX复合物对A549细胞的细胞毒性比游离DOX更大，因为低浓度负载的DOX（10μg/mL）与低剂量的X射线可导致肿瘤细胞完全凋亡。这项工作表明，负载DOX的O-TiO纳米片的治疗效果强烈依赖于其负载模式，并且在X射线照射下化疗和光动力疗法的效果增强，这使得O-TiO纳米片可作为光激活药物载体。这项工作为制备用于生物医学应用的二维金属氧化物纳米片提供了一种新策略。
