FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro

FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro
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FePt-Cys 纳米粒子诱导 ROS 依赖性细胞毒性,并增强 NSCLC 细胞体内和体外的化学放射敏感性

DOI:
10.1016/j.canlet.2018.01.024
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发表时间:
2018-04-01
期刊:
影响因子:
9.7
通讯作者:
Xie, Conghua
Xie, Conghua
中科院分区:
医学1区
文献类型:
--
作者:
Sun, Yingming;Miao, Hongtao;Xie, Conghua

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FePt-Cys纳米颗粒(FePt-Cys NPs)尽管其溶解度和稳定性较差,但在许多领域得到了广泛的应用。合成了半胱氨酸表面修饰的FePt NPs,具有良好的溶解性、稳定性和生物相容性。我们深入探讨了这种新型纳米颗粒系统在肺癌细胞中的抗肿瘤作用机制。在体外研究中,FePt-Cys NPs诱导活性氧(ROS)爆发,抑制抗氧化蛋白表达,诱导细胞凋亡。此外,FePt-Cys NPs可以阻止H1975和A549细胞的迁移和侵袭。这些变化与MMP-2/9表达的急剧下降和细胞附着增强有关。我们证明了FePt-Cys NPs通过激活caspase系统和损伤DNA损伤修复来促进化学辐射的作用。在体内研究中,未观察到严重过敏或药物相关死亡,FePt-Cys NPs与顺铂和放疗显示协同作用。综上所述,FePt-Cys NPs具有良好的安全性和有效性,因此可能成为放化疗的潜在增敏剂。(C) 2018 Elsevier B.V.版权所有
FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite their poor solubility and stability. We synthetized a cysteine surface modified FePt NPs, which exhibited good solubility, stability and biocompatibility. We explored the insight mechanisms of the antitumor effects of this new nanoparticle system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a reactive oxygen species (ROS) burst, which suppressed the antioxidant protein expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the migration and invasion of H1975 and A549 cells. These changes were correlated with a dramatic decrease in MMP-2/9 expression and enhanced the cellular attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair. In the in vivo study, no severe allergies or drug related deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy. (C) 2018 Elsevier B.V. All rights reserved.