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通过在癌症治疗中共同递送产生活性氧的纳米机器克服多药耐药性。

Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics.

作者信息

Kankala Ranjith Kumar, Tsai Pei-Yu, Kuthati Yaswanth, Wei Pei-Ru, Liu Chen-Lun, Lee Chia-Hung

机构信息

Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, 974, Taiwan.

出版信息

J Mater Chem B. 2017 Feb 21;5(7):1507-1517. doi: 10.1039/c6tb03146c. Epub 2017 Feb 1.

Abstract

The use of nanotechnology to overcome multidrug resistance (MDR) in cancer cells has been predominant. Herein, we report the conjugation of copper(ii)-doxorubicin complexes on the surfaces of layered double hydroxide nanoparticles (LDHs) along with ascorbic acid intercalation in the gallery space to demonstrate synergistic effects to conquer MDR. The pH-sensitive release of doxorubicin (Dox) and the sustained release of ascorbic acid (AA) generate high amounts of hydrogen peroxide intracellularly that concomitantly results in conversion to cytotoxic free radicals through a copper(ii)-catalyzed Fenton-like reaction. Therefore, the combination of the chemotherapeutic agent (Dox) and free radical attack can devastate the MDR for effective cancer treatment through the co-delivery system.

摘要

利用纳米技术克服癌细胞中的多药耐药性(MDR)一直占据主导地位。在此,我们报道了将铜(II)-阿霉素复合物缀合在层状双氢氧化物纳米颗粒(LDHs)表面,并在层间空间插入抗坏血酸,以证明其协同作用来攻克多药耐药性。阿霉素(Dox)的pH敏感释放和抗坏血酸(AA)的持续释放会在细胞内产生大量过氧化氢,通过铜(II)催化的类芬顿反应,这些过氧化氢会随之转化为细胞毒性自由基。因此,化疗药物(Dox)与自由基攻击的结合可以通过共递送系统破坏多药耐药性,从而实现有效的癌症治疗。

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