Dai Zideng, Song Xue-Zhi, Cao Junkai, He Yunping, Wen Wen, Xu Xinyu, Tan Zhenquan
School of Petroleum and Chemical Engineering, Dalian University of Technology Panjin 124221 P. R. China
RSC Adv. 2018 Jun 14;8(39):21975-21984. doi: 10.1039/c8ra02899k. eCollection 2018 Jun 13.
Biological applications of nanosheets are rapidly increasing currently, which introduces new possibilities to improve the efficacy of cancer chemotherapy and radiotherapy. Herein, we designed and synthesized a novel nano-drug system, doxorubicin (DOX) loaded titanium peroxide (TiO ) nanosheets, toward the synergistic treatment of lung cancer. The precursor of TiO nanosheets with high specific surface area was synthesized by a modified hydrothermal process using the polymer P123 as a soft template to control the shape. TiO nanosheets were obtained by oxidizing TiO nanosheets with HO. The anti-cancer drug DOX was effectively loaded on the surface of TiO nanosheets. Generation of reactive oxygen species, including HO, ·OH and ·O , was promoted from TiO nanosheets under X-ray irradiation, which is effective for cancer radiotherapy and drug release in cancer cells. In this way, chemotherapy and radiotherapy were combined effectively for the synergistic therapy of cancers. Our results reinforce the DOX loaded TiO nanosheets as a pH sensitive and X-ray controlled dual-stimuli-responsive drug release system. The cytotoxicity, cellular uptake, and intracellular location of the formulations were evaluated in the A549 human non-small cell lung cancer cell line. Our results showed that TiO /DOX complexes exhibited a greater cytotoxicity toward A549 cells than free DOX. This work demonstrates that the therapeutic efficacy of DOX-loaded TiO nanosheets is strongly dependent on their loading mode and the chemotherapeutic and radiotherapy effect is improved under X-ray illumination, which provides a significant breakthrough for future applications of TiO as a light activated drug carrier in cancer chemotherapy and radiotherapy.
目前，纳米片的生物应用正在迅速增加，这为提高癌症化疗和放疗的疗效带来了新的可能性。在此，我们设计并合成了一种新型纳米药物系统，即负载阿霉素（DOX）的过氧化钛（TiO ）纳米片，用于肺癌的协同治疗。以聚合物P123为软模板，通过改进的水热法合成了具有高比表面积的TiO纳米片前驱体，以控制其形状。通过用HO氧化TiO纳米片获得TiO 纳米片。抗癌药物DOX有效地负载在TiO 纳米片的表面。在X射线照射下，TiO 纳米片促进了包括HO、·OH和·O 在内的活性氧的产生，这对癌细胞的放疗和药物释放有效。通过这种方式，化疗和放疗有效地结合用于癌症的协同治疗。我们的结果强化了负载DOX的TiO 纳米片作为一种pH敏感和X射线控制的双刺激响应药物释放系统。在A549人非小细胞肺癌细胞系中评估了制剂的细胞毒性、细胞摄取和细胞内定位。我们的结果表明，TiO /DOX复合物对A549细胞的细胞毒性比游离DOX更大。这项工作表明，负载DOX的TiO 纳米片的治疗效果强烈依赖于其负载模式，并且在X射线照射下化疗和放疗效果得到改善，这为TiO 作为光活化药物载体在癌症化疗和放疗中的未来应用提供了重大突破。
