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

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...

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Bibliographic Details
Published in:Cancer letters 2018-04, Vol.418, p.27-40
Main Authors: Sun, Yingming, Miao, Hongtao, Ma, Shijing, Zhang, Lei, You, Chengcheng, Tang, Fang, Yang, Cui, Tian, Xiaoli, Wang, Feng, Luo, Yuan, Lin, Xiangjie, Wang, Hui, Li, Chunyang, Li, Zhijun, Yu, Hongnv, Liu, Xuefeng, Xiao, Yu, Gong, Yan, Zhang, Junhong, Quan, Hong, Xie, Conghua
Format: Article
Language:English
Subjects:
Antioxidants
Antitumor activity
Apoptosis
Biocompatibility
Cancer therapies
Caspase
Chemical elements
Chemo-radiation sensitivity
Chemoradiotherapy
Chemotherapy
Cisplatin
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Drug dosages
Ethanol
Extracellular matrix
FePt-Cys nanoparticles
Fourier transforms
Gelatinase A
Iron compounds
Ligands
Lung cancer
Morphology
Nanoparticles
Non-small cell lung carcinoma
Platinum compounds
Radiation
Radiation therapy
Reactive oxygen species
ROS
Solubility
Spectrum analysis
Surface stability
Toxicity
Tumors
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Summary: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. FePt-Cys Nanoparticles induce ROS-dependent cell toxicity, and enhance chemo-radiation sensitivity of NSCLC cells in vivo and in vitro. [Display omitted] •FePt-Cys NPs are a novel nanoparticle system with good water-solubility, dispersity and biocompatibility.•FePt-Cys NPs have a synergistic effect with radiotherapy by impairing DNA damage repair.•FePt-Cys NPs promote chemotherapy effect by activating caspase-dependent apoptosis.•FePt-Cys NPs inhibit NSCLC cell invasion and migration by downregulating metalloproteases and enhancing cell adhesion.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2018.01.024