Chen Ching-Wen, Syu Wei-Jhe, Huang Tzu-Chi, Lee Yao-Chang, Hsiao Jong-Kai, Huang Kuo-Yi, Yu Hsiu-Ping, Liao Mei-Yi, Lai Ping-Shan
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan.
J Mater Chem B. 2017 Aug 7;5(29):5774-5782. doi: 10.1039/c7tb00944e. Epub 2017 Jul 7.
The combination of the functions of near infrared-triggered molecule release and chemo-photothermal therapy improved the therapeutic effect, but clarification of the cancer damage pathway in terms of protein molecule levels has yet to be well studied. In this study, we developed a polymer encapsulation synthesis of Au/FeO@polymer nanoparticles as a Swiss army knife to integrate near infrared absorption, magnetism, and doxorubicin (DOX) loading ability into a single package. By exposing to near infrared absorption, the Au/FeO@polymer nanoparticles possessed photothermal therapy, exhibiting anti-tumor growth suppression of HT-29 tumor-bearing nude mice with less body weight loss. To deeply understand the interactions between the drug-loaded nanocarriers and the protein structures of the treated cells, delivering therapeutic DOX agent combined with photothermal therapy with Au/FeO@polymer nanostructures to cancer cells was investigated. Synchrotron-based FTIR imaging and confocal imaging showed direct observation of the efficient photo-chemotherapy impacting MCF7, MCF7/ADR, and HT-29 cells after the near infrared radiation-triggered DOX release. Our demonstration outlines how the cell destruction in the molecular mechanism was initiated by chemo-photothermal combination therapy after the translocation of DOX from the cytosol to the nuclei, leading to altered intracellular secondary proteins. For preclinical application of potential diagnosis to cancer cells, Au/FeO@polymer nanoparticles performed integrated computed tomography/magnetic resonance imaging contrast enhancement and near infrared-triggered chemo-photothermal therapy.
近红外触发分子释放功能与化学光热疗法的结合提高了治疗效果,但从蛋白质分子水平阐明癌症损伤途径尚未得到充分研究。在本研究中,我们开发了一种聚合物封装合成的Au/FeO@聚合物纳米颗粒,作为一种多功能工具,将近红外吸收、磁性和阿霉素(DOX)负载能力整合到一个单一的组件中。通过近红外吸收,Au/FeO@聚合物纳米颗粒具备光热疗法,对荷HT-29肿瘤裸鼠表现出抗肿瘤生长抑制作用,且体重减轻较少。为了深入了解载药纳米载体与处理后细胞蛋白质结构之间的相互作用,研究了将治疗性DOX剂与Au/FeO@聚合物纳米结构的光热疗法相结合递送至癌细胞的情况。基于同步加速器的傅里叶变换红外成像和共聚焦成像显示,在近红外辐射触发DOX释放后,可以直接观察到对MCF7、MCF7/ADR和HT-29细胞的有效光化学疗法。我们的论证概述了在DOX从细胞质转移到细胞核后,化学光热联合疗法如何在分子机制上引发细胞破坏,导致细胞内二级蛋白质发生改变。对于癌细胞潜在诊断的临床前应用,Au/FeO@聚合物纳米颗粒实现了计算机断层扫描/磁共振成像的综合对比增强以及近红外触发的化学光热疗法。