磷脂包覆金纳米棒对乳腺癌细胞系的细胞摄取、细胞毒性和细胞死亡方式的研究。

Insights into the Cellular Uptake, Cytotoxicity, and Cellular Death Modality of Phospholipid-Coated Gold Nanorods toward Breast Cancer Cell Lines.

机构信息

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

出版信息

Mol Pharm. 2019 Oct 7;16(10):4149-4164. doi: 10.1021/acs.molpharmaceut.9b00470. Epub 2019 Aug 23.

Abstract

Gold nanorods (GNRs) have gained pronounced recognition in the diagnosis and treatment of cancers driven by their distinctive properties. Herein, a gold-based nanosystem was prepared by utilizing a phospholipid moiety linked to thiolated polyethylene glycol, 1,2-distearoyl--glycero-3-phosphoethanolamine--PEG-SH, as a surface decorating agent. The synthesized phospholipid-PEG-GNRs displayed good colloidal stability upon exposure to the tissue culture medium. Cytotoxicity of phospholipid-PEG-GNRs was investigated toward MCF-7 and T47D breast cancer cells using sulforhodamine B test. The results revealed that phospholipid-PEG-GNRs demonstrated  high cytotoxicity to MCF-7 cells compared to T47D cells, and minimal cytotoxicity to human dermal fibroblasts. The cellular uptake studies performed by imaging and quantitative analysis demonstrated  massive internalization of phospholipid-coated GNRs into  MCF-7 cells in comparison to T47D cells. The cellular death modality of cancer cells after treatment with phospholipid-PEG-GNRs was evaluated using mitochondrial membrane potential assay (JC-1 dye), gene expression analysis, and flow cytometry study. The overall results suggest that phospholipid-modified GNRs enhanced mainly the cellular apoptotic events in MCF-7 cells in addition to necrosis, whereas cellular necrosis and suppression of cellular invasion contributed to the cellular death modality in the T47D cell line upon treatment with phospholipid-PEG-GNRs. The phospholipid-coated GNRs interact in a different manner with breast cancer cell lines and could be considered for breast cancer treatment.

摘要

金纳米棒(GNRs)因其独特的性质在癌症的诊断和治疗中得到了广泛的认可。在此,通过利用连接到巯基化聚乙二醇的磷脂部分,1,2-二硬脂酰基-甘油-3-磷酸乙醇胺-PEG-SH,制备了一种基于金的纳米系统。合成的磷脂-PEG-GNRs 在暴露于组织培养基时表现出良好的胶体稳定性。使用磺基罗丹明 B 试验研究了磷脂-PEG-GNRs 对 MCF-7 和 T47D 乳腺癌细胞的细胞毒性。结果表明,与 T47D 细胞相比,磷脂-PEG-GNRs 对 MCF-7 细胞表现出高细胞毒性,对人真皮成纤维细胞的细胞毒性最小。通过成像和定量分析进行的细胞摄取研究表明,与 T47D 细胞相比,大量带磷脂的 GNRs 被内化到 MCF-7 细胞中。用线粒体膜电位测定法(JC-1 染料)、基因表达分析和流式细胞术研究评估了用磷脂-PEG-GNRs 处理后癌细胞的细胞死亡方式。总的来说,这些结果表明,磷脂修饰的 GNRs 除了坏死之外,还主要增强了 MCF-7 细胞中的细胞凋亡事件,而细胞坏死和抑制细胞侵袭导致 T47D 细胞系在磷脂-PEG-GNRs 处理后发生细胞死亡方式。带磷脂的 GNRs 以不同的方式与乳腺癌细胞系相互作用,可用于乳腺癌治疗。

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