Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China.
Int J Nanomedicine. 2013;8:1835-41. doi: 10.2147/IJN.S43657. Epub 2013 May 8.
Nanomaterials have emerged as ideal multimodal nanomedicine platforms, each one combining different designs and therapeutic approaches in a single system against cancer. The aim of the current study was to explore the synergistic effect and mechanism of a doxorubicin (Dox)-ZnO nanocomplex as a multimodal drug delivery system, integrating Dox chemotherapy and ZnO-mediated photodynamic therapy, in anticancer therapeutics.
Dox was loaded onto ZnO nanomaterials, forming complexes with the transition metal Zn to yield the Dox-ZnO nanocomplexes. After culture with SMMC-7721 hepatocarcinoma cells, the cellular uptake was quantitatively detected by flow cytometry and visualized by fluorescence microscopy. The synergistic effects of the different anticancer therapeutic modalities on the proliferation of SMMC-7721 hepatocarcinoma cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of B-cell lymphoma 2 protein (Bcl-2), Bcl-2 associated X protein (Bax), caspase 9, and caspase 3 were examined by Western blot, to elucidate the possible molecular mechanisms involved.
Our observations demonstrated that Dox-ZnO nanocomplexes could act as an efficient drug delivery system for importing Dox into SMMC-7721 cells, enhancing its potential chemotherapy efficiency by increasing the intracellular concentration of Dox. With the addition of ultraviolet (UV) illumination, the ZnO nanomaterials showed excellent photodynamic therapeutic properties, attacking the cancer cells further. Thus the caspase-dependent apoptosis was synergistically induced, resulting in distinct improvement in anticancer activity.
The Dox-ZnO nanocomplex presents a promising multimodal agent for comprehensive cancer treatment.
纳米材料已成为理想的多模式纳米医学平台，每个平台都将不同的设计和治疗方法结合在一个单一的系统中，用于治疗癌症。本研究旨在探讨阿霉素（Dox）-ZnO 纳米复合物作为一种多模式药物输送系统的协同作用和机制，该系统将 Dox 化学疗法和 ZnO 介导的光动力疗法结合在一起，用于癌症治疗。
将 Dox 加载到 ZnO 纳米材料上，与过渡金属 Zn 形成复合物，得到 Dox-ZnO 纳米复合物。用 SMMC-7721 肝癌细胞培养后，用流式细胞术定量检测细胞摄取，并通过荧光显微镜观察。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）试验评估不同抗癌治疗方式对 SMMC-7721 肝癌细胞增殖的协同作用。通过 Western blot 检测 B 细胞淋巴瘤 2 蛋白（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）、半胱天冬酶 9 和半胱天冬酶 3 的表达，以阐明可能涉及的分子机制。
我们的观察结果表明，Dox-ZnO 纳米复合物可作为将 Dox 导入 SMMC-7721 细胞的有效药物输送系统，通过增加 Dox 的细胞内浓度来提高其潜在的化学治疗效率。加入紫外线（UV）照射后，ZnO 纳米材料表现出优异的光动力治疗性能，进一步攻击癌细胞。因此， caspase 依赖性细胞凋亡被协同诱导，导致抗癌活性明显改善。
Dox-ZnO 纳米复合物是一种有前途的综合癌症治疗多模式药物。
