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Synthesis of 2-deoxy-D-glucose coated Fe3O4 nanoparticles for application in targeted delivery of the Pt(IV) prodrug of cisplatin – a novel approach in chemotherapy
New Journal of Chemistry ( IF 2.7 ) Pub Date : 2020-07-13 , DOI: 10.1039/c9nj05989j
K. Shitaljit Sharma 1, 2, 3, 4 , Akhil K. Dubey 2, 3, 4, 5 , Arunkumar S. Koijam 2, 3, 4, 6 , Chandan Kumar 2, 3, 4, 6 , Anand Ballal 2, 3, 4, 7 , Sudip Mukherjee 3, 4, 8, 9 , Prasad P. Phadnis 1, 2, 3, 4, 10 , Rajesh K. Vatsa 1, 2, 3, 4, 10
Affiliation  

A water soluble Pt(IV) prodrug of cisplatin was synthesized by oxidation of cisplatin followed by treatment with succinic anhydride to achieve easily reducible ester linkage at axial positions which was evidenced from cyclic voltammetric analyses. Because of this modification the Pt(IV) prodrug achieved better physicochemical and pharmacological properties like water solubility and reduced toxicity for normal (non-cancerous) CHO cells respectively, as compared to cisplatin. Later, this Pt(IV) prodrug was loaded on 2-deoxy-D-glucose (2DG) functionalized over silica coated Fe3O4 magnetic nanoparticles (MNPs) to achieve the desired formulation. It exhibited potency as evidenced from the cytotoxicity evaluation against MCF-7 human breast cancer cell lines (IC50 ∼ 14 μM). This encouraged us to further study the percentage viability, apoptosis and cell death evaluations on MCF-7, Colo-205 and CHO cells by flow cytometry. The cytotoxic potency of the formulation towards cancer cells, Colo-205 and MCF-7 (22–30% apoptosis), was revealed while the parent formulation was non-toxic to non-cancerous, CHO cell lines (3% apoptosis) as compared to cisplatin. It revealed that the formulation is comparable to cisplatin in its cell killing efficiency. Additionally the FITC labeled MNPs coated with 2DG exhibited efficient cell uptake and fast internalization (within 3 h) accumulating mainly in the cytoplasm and at the cell surface. Besides this, the formulation exhibited heating efficacy suggesting its possible application for hyperthermia treatment also. These results indicate the possible utility of the formulation for site specific delivery of the Pt(IV) prodrug of cisplatin.

中文翻译:

合成2-脱氧-D-葡萄糖涂层的Fe3O4纳米粒子,用于顺铂Pt(IV)前药的靶向递送–一种化学疗法的新方法

通过顺铂的氧化,然后用琥珀酸酐处理以在轴向位置实现容易还原的酯键合,合成了顺铂的水溶性Pt(IV)前药,这由循环伏安法分析证明。由于这种修饰,与顺铂相比,Pt(IV)前药分别获得了更好的理化和药理特性,例如水溶性和对正常(非癌性)CHO细胞的毒性降低。随后,将这种Pt(IV)前药加载到在二氧化硅涂覆的Fe 3 O 4上官能化的2-deoxy- D-葡萄糖(2DG)磁性纳米粒子(MNP)以获得所需的配方。从针对MCF-7人乳腺癌细胞系的细胞毒性评估中可以看出,它具有强大的效力(IC 50约14μM)。这鼓励我们通过流式细胞术进一步研究MCF-7,Colo-205和CHO细胞的存活率百分比,凋亡和细胞死亡评估。揭示了该制剂对癌细胞Colo-205和MCF-7的细胞毒性潜能(22-30%凋亡),而母体制剂对非癌性CHO细胞系无毒(凋亡3%)。顺铂。结果表明,该制剂在细胞杀伤效率上可与顺铂媲美。此外,涂有2DG的FITC标记的MNPs表现出有效的细胞摄取和快速内在化(3小时内),主要在细胞质和细胞表面积累。除此之外,该制剂还显示出加热功效,表明其也可能用于热疗。IV)顺铂前药。
更新日期:2020-08-17
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