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新型功能化硒纳米颗粒用于增强体外抗肝癌活性

Novel Functionalized Selenium Nanoparticles for Enhanced Anti-Hepatocarcinoma Activity In vitro.

作者信息

Xia Yu, You Pengtao, Xu Fangfang, Liu Jing, Xing Feiyue

机构信息

Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, 510632, People's Republic of China.

出版信息

Nanoscale Res Lett. 2015 Dec;10(1):1051. doi: 10.1186/s11671-015-1051-8. Epub 2015 Sep 3.

Abstract

Selenium nanoparticles loaded with an anticancer molecule offer a new strategy for cancer treatment. In the current study, anisomycin-loaded functionalized selenium nanoparticles (SeNPs@Am) have been made by conjugating anisomycin to the surface of selenium nanoparticles to improve anticancer efficacy. The prepared nanoparticles were fully characterized by transmission electronic microscopy, energy dispersive X-ray spectroscopy, Fourier-transformed infrared spectroscopy, and X-ray photoelectron spectroscopy. The results showed that anisomycin was successfully conjugated with selenium nanoparticles. The size of particles could be effectively regulated through altering the reaction concentrations of sodium selenite and anisomycin. The SeNPs@Am particles (56 nm) exhibited the greatest capacity for cellular uptake. The further study showed that SeNPs@Am entered human hepatocellular carcinoma HepG2 cells in a dose or time-dependent manner via macropinocytosis and clathrin-mediated endocytosis pathways. SeNPs@Am significantly inhibited HepG2 cell proliferation with the low cytotoxicity against normal cells, and dramatically precluded the aggression and migration of HepG2 cells. It also arrested the cell cycle progression at the G0/G1 phase through the activation of the cyclin-dependent kinase inhibitors with inhibition of CDK-2 and ICBP90, and induced the cell apoptosis through activating the caspase cascade signaling in HepG2 cells, markedly superior to anisomycin alone. The findings indicate that SeNPs@Am may be a promising drug for hepatocellular carcinoma.

摘要

负载抗癌分子的硒纳米颗粒为癌症治疗提供了一种新策略。在当前研究中,通过将茴香霉素缀合到硒纳米颗粒表面以提高抗癌功效,制备了负载茴香霉素的功能化硒纳米颗粒(SeNPs@Am)。通过透射电子显微镜、能量色散X射线光谱、傅里叶变换红外光谱和X射线光电子能谱对制备的纳米颗粒进行了全面表征。结果表明,茴香霉素成功地与硒纳米颗粒缀合。通过改变亚硒酸钠和茴香霉素的反应浓度,可以有效地调节颗粒大小。SeNPs@Am颗粒(56 nm)表现出最大的细胞摄取能力。进一步研究表明,SeNPs@Am通过巨胞饮作用和网格蛋白介导的内吞途径以剂量或时间依赖性方式进入人肝癌HepG2细胞。SeNPs@Am显著抑制HepG2细胞增殖,对正常细胞的细胞毒性较低,并显著抑制HepG2细胞的侵袭和迁移。它还通过激活细胞周期蛋白依赖性激酶抑制剂并抑制CDK-2和ICBP90,使细胞周期进程停滞在G0/G1期,并通过激活HepG2细胞中的半胱天冬酶级联信号诱导细胞凋亡,明显优于单独使用茴香霉素。这些发现表明,SeNPs@Am可能是一种有前途的肝癌治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9647/4558992/54afc670830b/11671_2015_1051_Fig1_HTML.jpg

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