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新型纳米递送系统用于将金纳米粒子上的芳樟醇负载于 CALNN 肽,用于药物摄取和诱导乳腺癌细胞系细胞死亡的应用。

Novel of nano delivery system for Linalool loaded on gold nanoparticles conjugated with CALNN peptide for application in drug uptake and induction of cell death on breast cancer cell line.

机构信息

Division of Biotechnology, Department of Applied Science, University of Technology, Baghdad, Iraq.

Division of Biotechnology, Department of Applied Science, University of Technology, Baghdad, Iraq.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Jan 1;94:949-964. doi: 10.1016/j.msec.2018.10.014. Epub 2018 Oct 13.

Abstract

Linalool is a monoterpene alcohol which occurs naturally in several aromatic plants. The aims of this study are to load Linalool on gold nanoparticles, conjugate the complex with CALNN peptide, and investigate them for in-vitro anticancer activities against breast cancer (MCF-7) cell line. Linalool was obtained with 98% purity while gold nanoparticles and CALNN peptide were chemically synthesized. The formation of LIN-GNPs and LIN-GNPs-CALNN was observed through a color change. These compounds were confirmed and characterized using SEM, DLS, AFM, UV-VIS spectrophotometer, XRD, and FTIR. The free radical scavenging potential of each compound was confirmed based on its stable antioxidant effects using different parameters. Blood compatibility on red blood cells was confirmed by hemolytic and in vitro cytotoxicity assays. The in-vitro anticancer activity of each compound towardMCF-7 cell line was investigated using various parameters. From the results, Linalool, GNPs, LIN-GNPs, and LIN-GNPs-CALNN were found to exert cell growth arrest against MCF-7 cell line. The anti-proliferative effect of these compounds was due to cell death and induction of apoptosis confirmed using acridine orange-Ethidium bromide dual staining, DAPI staining, and electrophoresis analysis of DNA fragmentation. High fluorescent signals specific for the cellular uptake of LIN-GNPs and LIN-GNPs-CALNN into the cytoplasm of the cell line were confirmed. To study the toxicity of LIN-GNPs-CALNN in animal models, the hematological, histopathological, and body weight changes were estimated after 4 weeks of intraperitoneal injection of the compounds into the animal models. Our results demonstrate that Linalool, GNPs, Linalool-GNPs, and Linalool-GNPs-CALNN peptide had no side effects and could be clinically used for future therapeutic purposes.

摘要

芳樟醇是一种单萜醇,天然存在于几种芳香植物中。本研究的目的是将芳樟醇负载到金纳米粒子上,将该复合物与 CALNN 肽缀合,并研究其对乳腺癌(MCF-7)细胞系的体外抗癌活性。芳樟醇的纯度为 98%,而金纳米粒子和 CALNN 肽是通过化学合成得到的。通过颜色变化观察到 LIN-GNPs 和 LIN-GNPs-CALNN 的形成。通过 SEM、DLS、AFM、UV-VIS 分光光度计、XRD 和 FTIR 对这些化合物进行了确认和表征。根据其稳定的抗氧化作用,通过不同参数确认了每种化合物的自由基清除潜力。通过溶血和体外细胞毒性测定来确认对红细胞的血液相容性。通过各种参数研究了每种化合物对 MCF-7 细胞系的体外抗癌活性。结果表明,芳樟醇、GNPs、LIN-GNPs 和 LIN-GNPs-CALNN 对 MCF-7 细胞系的生长有抑制作用。这些化合物的抗增殖作用是由于细胞死亡和诱导细胞凋亡所致,这通过吖啶橙-溴化乙锭双重染色、DAPI 染色和 DNA 片段电泳分析得到证实。证实了 LIN-GNPs 和 LIN-GNPs-CALNN 对细胞的高荧光信号特异性摄取进入细胞系的细胞质。为了研究 LIN-GNPs-CALNN 在动物模型中的毒性,在向动物模型腹腔内注射化合物 4 周后,评估了血液学、组织病理学和体重变化。我们的结果表明,芳樟醇、GNPs、芳樟醇-GNPs 和芳樟醇-GNPs-CALNN 肽没有副作用,可以用于未来的治疗目的。

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