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Thionine Conjugated Gold Nanoparticles Trigger Apoptotic Activity Toward HepG2 Cancer Cell Line
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2018-01-03 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00390
Puja Paul 1, 2 , Sabyasachi Chatterjee 1 , Arindam Pramanik 3 , Parimal Karmakar 3 , Subhash Chandra Bhattacharyya 2 , Gopinatha Suresh Kumar 1
Affiliation  

Cancer cells were locally damaged using targeted gold nanoparticles (GNP) conjugated with therapeutic dye thionine (TN). GNP was prepared by citrate reduction method, and the two complexes, namely GTN1 and GTN2, were synthesized by mixing GNP and TN at different ratios at room temperature and at 80 °C, respectively. It is expected that GTN1 is formed when stabilizer TN participates in the reduction of Au3+ ions to Au0 nanocrystallites, while GTN2 is synthesized when the cationic dye TN adsorbs onto the GNP surfaces due to the electrostatic attraction. The compounds were characterized by strong plasmon resonance absorption, Fourier transform infrared spectroscopy, dynamic light scattering technique, ζ-potential measurement, transmission electron microscopy, and atomic force microscopy. Crystallinity of the NPs was ascertained by X-ray diffraction. Strong binding of GTN1 to DNA and the structural perturbation prompted us to study the cytotoxic activity of the compounds on hepatocellular carcinoma cell lines (HepG2) by MTT assay. The mode of cytotoxicity was found due to reactive oxygen species (ROS) generation inside the cells. Fluorescence microscopy analysis revealed nuclear fragmentation which was caused due to the ROS. The GTN1 induced fragmentation led to the apoptosis mediated cell death as found from the cell cycle study. Conclusions drawn from these studies emphasized GTN1 to be capable of inhibiting proliferation in cancer cells in an amount greater than that of other compounds. The importance of the work lies in the exploration of effectiveness of nanoparticles to prevent cancer cell proliferation, which is a progressive step toward novel biomedical applications.

中文翻译:

硫氨酸结合的金纳米颗粒触发对HepG2癌细胞系的凋亡活性。

使用与治疗性染料硫氨酸(TN)偶联的靶向金纳米颗粒(GNP)局部破坏癌细胞。用柠檬酸盐还原法制备GNP,并分别在室温和80°C下以不同比例混合GNP和TN,合成出两种复合物,即GTN1和GTN2。预计当稳定剂TN参与将Au 3+离子还原为Au 0时会形成GTN1。纳米微晶,而当阳离子染料TN由于静电吸引而吸附到GNP表面时,就会合成GTN2。这些化合物的特征在于强等离振子共振吸收,傅立叶变换红外光谱,动态光散射技术,ζ电位测量,透射电子显微镜和原子力显微镜。NP的结晶度通过X射线衍射确定。GTN1与DNA的强结合以及结构扰动促使我们通过MTT分析研究化合物对肝癌细胞系(HepG2)的细胞毒活性。由于细胞内活性氧(ROS)的产生,发现了细胞毒性的模式。荧光显微镜分析显示核碎裂是由于ROS引起的。从细胞周期研究中发现,GTN1诱导的断裂导致凋亡介导的细胞死亡。从这些研究得出的结论强调,GTN1能够以比其他化合物更大的量抑制癌细胞的增殖。这项工作的重要性在于探索纳米颗粒预防癌细胞增殖的有效性,这是向新型生物医学应用迈进的一步。
更新日期:2018-01-03
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