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载亚麻醇的谷胱甘肽修饰金纳米粒子与 CALNN 肽缀合作为 SKOV-3 细胞系中凋亡诱导剂和 NF-κB 易位抑制剂。

Linalool-Loaded Glutathione-Modified Gold Nanoparticles Conjugated with CALNN Peptide as Apoptosis Inducer and NF-κB Translocation Inhibitor in SKOV-3 Cell Line.

机构信息

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

University of Misan, Department of Basic Science, Misan, Iraq.

出版信息

Int J Nanomedicine. 2020 Nov 17;15:9025-9047. doi: 10.2147/IJN.S276714. eCollection 2020.

Abstract

BACKGROUND

Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability.

METHODS

We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis.

RESULTS

Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone.

CONCLUSION

We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.

摘要

背景

芳樟醇是一种单萜化合物,在多个医学领域具有各种潜在的治疗应用。先前的研究表明芳樟醇对细胞系具有活性;然而,其高毒性限制了它的使用。本研究的目的是设计和制造具有新型结构的化合物,可用于负载芳樟醇,以降低其毒性并提高其可达性。

方法

我们合成并表征了一种新的分子,用于将芳樟醇负载到金纳米颗粒(GNPs)上,这些颗粒被谷胱甘肽覆盖,并与 CALNN 肽结合。芳樟醇通过芳樟醇和 GNPs 的表面基团之间的反应被负载到 GNPs 上。此外,目标肽可以通过化学反应被负载到 GNPs 的表面上。研究了芳樟醇-GNP(LG)和芳樟醇-GNP-CALNN 肽(LGC)缀合物对卵巢癌细胞的细胞毒性作用,以及诱导细胞凋亡的可能机制。

结果

我们的研究结果表明,LG 和 LGC 对 SKOV-3 细胞具有显著的抗增殖作用。细胞毒性测定表明,LG 和 LGC 对癌细胞具有选择性毒性,并通过激活半胱天冬酶-8、p53 蛋白和参与凋亡的各种蛋白诱导细胞凋亡。本研究数据表明,LG 和 LGC 具有很高的治疗潜力,应特别考虑将其作为抗癌药物输送系统,因为 LG 和 LGC 对癌细胞系的细胞毒性明显高于芳樟醇和 GNPs 单独使用。

结论

我们得出结论,LG 和 LGC 是有前途的化合物,可通过外源性和内源性途径诱导细胞凋亡来治疗卵巢癌(SKOV-3)细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb4/7680166/e8eb54485b1f/IJN-15-9025-g0001.jpg

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