Photothermal Treatment of Human Pancreatic Cancer Using PEGylated Multi-Walled Carbon Nanotubes Induces Apoptosis by Triggering Mitochondrial Membrane Depolarization Mechanism.
Photothermal Treatment of Human Pancreatic Cancer Using PEGylated Multi-Walled Carbon Nanotubes Induces Apoptosis by Triggering Mitochondrial Membrane Depolarization Mechanism.
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DOI：
10.7150/jca.9481
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发表时间：
2014
影响因子：
3.9
通讯作者：
Mocan L
中科院分区：
文献类型：
--
作者：
Mocan T;Matea CT;Cojocaru I;Ilie I;Tabaran FA;Zaharie F;Iancu C;Bartos D;Mocan L
胰腺癌（PC）是人类最致命的实体瘤之一，总体5年生存率低于5%。热活性碳纳米管已经在 PC 研究和治疗领域取得了有希望的成果。我们在此报告了基于多壁碳纳米管和聚乙二醇（PEG）分子的纳米生物系统的构建，并通过 AFM、UV-Vis 和 DLS 进行了验证。接下来，我们研究了这些 PEG 化的多壁碳纳米管（分别为 5、10 和 50 μg/mL）对胰腺癌细胞 (PANC-1) 的光热效应，并进一步分析了细胞死亡发生中涉及的分子和细胞事件。利用 ELISA、荧光显微镜和流式细胞术的细胞增殖、凋亡、膜极化和氧化应激测定，我们在此表明，MWCNTs-PEG 激光介导的治疗（808 nm，2W）后的高温会导致线粒体膜去极化，从而激活细胞内自由基的通量，氧化状态通过凋亡途径介导 PC 细胞中的细胞损伤。我们的结果具有决定性的重要性，特别是在开发能够靶向线粒体并协同发挥细胞毒性药物和热活性剂作用的新型纳米生物系统方面，以克服肿瘤学中最常见的问题之一，即对化疗药物的内在耐药性。
Pancreatic cancer (PC) is one of the most lethal solid tumor in humans, with an overall 5-year survival rate of less than 5%. Thermally active carbon nanotubes have already brought to light promising results in PC research and treatment. We report here the construct of a nano-biosystem based on multi-walled carbon nanotubes and polyethylene glycol (PEG) molecules validated through AFM, UV-Vis and DLS. We next studied the photothermal effect of these PEG-ylated multi-walled carbon nanotubes (5, 10 and 50 μg/mL, respectively) on pancreatic cancer cells (PANC-1) and further analyzed the molecular and cellular events involved in cell death occurrence. Using cell proliferation, apoptosis, membrane polarization and oxidative stress assays for ELISA, fluorescence microscopy and flow cytometry we show here that hyperthermia following MWCNTs-PEG laser mediated treatment (808 nm, 2W) leads to mitochondrial membrane depolarization that activates the flux of free radicals within the cell and the oxidative state mediate cellular damage in PC cells via apoptotic pathway. Our results are of decisive importance especially in regard with the development of novel nano-biosystems capable to target mitochondria and to synergically act both as cytotoxic drug as well as thermally active agents in order to overcome one of the most common problem met in oncology, that of intrinsic resistance to chemotherapeutics.
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影响因子：
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作者：
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