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胆固醇包被的金纳米棒作为一种用于化疗给药及乳腺癌潜在治疗的高效纳米载体:使用MCF-7细胞系的研究

Cholesterol-coated gold nanorods as an efficient nano-carrier for chemotherapeutic delivery and potential treatment of breast cancer: studies using the MCF-7 cell line.

作者信息

Mahmoud Nouf N, Sabbah Dima A, Abu-Dahab Rana, Abuarqoub Duaa, Abdallah Maha, Hasan Ibrahim Ameerah, Khalil Enam A

机构信息

Faculty of Pharmacy, Al-Zaytoonah University of Jordan Amman 11733 Jordan

School of Pharmacy, The University of Jordan Amman 11942 Jordan.

出版信息

RSC Adv. 2019 Apr 24;9(22):12718-12731. doi: 10.1039/c9ra01041f. eCollection 2019 Apr 17.

Abstract

Gold nanorods (GNRs) have a recognized role in treatment of cancers as efficient nanocarriers for chemotherapeutic drug delivery. In this study, GNRs modified with cholesterol-PEG were employed as a nanocarrier for a hydrophobic compound having a promising phosphatidylinositol 3-kinase (PI3Kα) inhibitory activity. The acquired nanocomplex was characterized by optical and infra-red (IR) absorption spectroscopies, in addition to hydrodynamic size and zeta potential. Glide docking and superposing of docked poses of the hydrophobic ligand and cholesterol moiety demonstrated that hydrophobic interactions drive the conjugation and attachment of the ligand to the cholesterol moiety of the nanocarrier. release study under a cellular environment indicates that the presence of cells has enhanced the release and the cellular uptake of the conjugated ligand. Furthermore, the anti-proliferative assay of the nanocomplex revealed potent cytotoxicity over a low concentration range of the nanocomplex against MCF-7 breast cancer cells compared to the free compound or the nanocarrier alone. Analysis of cellular death modality by flow cytometry showed that the nanocomplex has a rapid effect on cell death, as cells went toward the late apoptotic/necrotic stage rapidly and proportionally to the increase of the nanocomplex concentration. The overall results propose that cholesterol-decorated GNRs could be considered as a promising nanocarrier for hydrophobic drugs to achieve efficient delivery and potential therapy against breast cancer cells.

摘要

金纳米棒(GNRs)作为化疗药物递送的高效纳米载体,在癌症治疗中具有公认的作用。在本研究中,用胆固醇-聚乙二醇修饰的金纳米棒被用作一种具有潜在磷脂酰肌醇3激酶(PI3Kα)抑制活性的疏水化合物的纳米载体。除了流体动力学尺寸和zeta电位外,还通过光学和红外(IR)吸收光谱对获得的纳米复合物进行了表征。疏水配体和胆固醇部分对接构象的滑动对接和叠加表明,疏水相互作用驱动配体与纳米载体的胆固醇部分的共轭和附着。细胞环境下的释放研究表明,细胞的存在增强了共轭配体的释放和细胞摄取。此外,纳米复合物的抗增殖试验显示,与游离化合物或单独的纳米载体相比,在低浓度范围内,纳米复合物对MCF-7乳腺癌细胞具有强大的细胞毒性。通过流式细胞术分析细胞死亡方式表明,纳米复合物对细胞死亡有快速作用,因为细胞迅速进入晚期凋亡/坏死阶段,且与纳米复合物浓度的增加成比例。总体结果表明,胆固醇修饰的金纳米棒可被认为是一种有前途的疏水药物纳米载体,以实现对乳腺癌细胞的有效递送和潜在治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4327/9063807/fe47d35f990a/c9ra01041f-f1.jpg

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