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Zero-valent iron based nanoparticles selectively inhibit cancerous cells through mitochondria-mediated autophagy

机译:零价铁基纳米颗粒通过线粒体介导的自噬选择性抑制癌细胞

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How to improve the selectivity and efficacy of anticancer agents and to reduce side effects has always been a big challenge in clinical cancer therapy. Chemotherapeutic agents are usually toxic to both cancer and normal tissues, thus rendering compromised overall clinical outcome. Here we developed zero-valent iron nanoparticles (ZVI NPs) that exhibited selectivity toward higher toxicity to most cancerous cells thus opening a new era of anti-cancer therapy or adjuvant therapy through a novel molecular signaling pathway. We used head-and-neck cancer (HNC) cells and ovarian cancer (OVCA) cells to test the anti-cancer properties of ZVI NPs. The ZVI NPs served as a strong reactive oxygen species (ROS) inducer and caused irreversible mitochondria membrane potential lost in sensitive cancer cells that lead to cancer cell autophagy and growth suppression, while not significantly affect normal cell population. Further, the cytotoxicity of the ZVI NPs is highly depended on its redox state as oxidation of the NPs upon aging reduced their cytotoxic potency. In vivo study revealed a dose dependent tumor size reduction in tumor-bearing mice model without significant weight loss and pathological signs. These results suggest that ZVI NPs may serve as a new class of anticancer agent for a wide spectra of neoplastic diseases.
机译:如何提高抗癌药的选择性和功效以及减少副作用一直是临床癌症治疗中的一大挑战。化学治疗剂通常对癌症和正常组织均具有毒性,因此损害了整体临床结果。在这里,我们开发了零价铁纳米粒子(ZVI NPs),它对大多数癌细胞具有更高的毒性选择性,从而通过新型分子信号传导途径开辟了抗癌疗法或辅助疗法的新时代。我们使用头颈癌(HNC)细胞和卵巢癌(OVCA)细胞来测试ZVI NP的抗癌特性。 ZVI NPs作为强活性氧(ROS)诱导剂,在敏感癌细胞中造成不可逆的线粒体膜电位损失,从而导致癌细胞自噬和生长抑制,而不会显着影响正常细胞群体。此外,ZVI NP的细胞毒性高度依赖于其氧化还原状态,因为老化后NP的氧化降低了它们的细胞毒性。体内研究显示,荷瘤小鼠模型的肿瘤大小呈剂量依赖性降低,而体重和病理迹象却没有明显降低。这些结果表明,ZVI NPs可以作为一类新的抗癌剂,适用于广谱的肿瘤疾病。

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