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载有阿霉素的单壁碳纳米管的细胞毒性

Cytotoxicity of doxrubicin loaded single-walled carbon nanotubes.

作者信息

Ünlü Ayhan, Meran Mehdi, Dinc Bircan, Karatepe Nilgün, Bektaş Muhammet, Güner F Seniha

机构信息

Department of Biophysics, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.

Department of Chemical Engineering, Istanbul Technical University, 34469, Istanbul, Turkey.

出版信息

Mol Biol Rep. 2018 Aug;45(4):523-531. doi: 10.1007/s11033-018-4189-5. Epub 2018 May 24.

Abstract

Carbon nanotube (CNTs) is a new alternative for efficient drug delivery and it has a great potential to change drug delivery system profile in pharmaceutical industry. One of the important advantage of CNTs is their needle-like, cylindrical shape. This shape provides a high surface area for multiple connections and adsorption onto for millions of therapeutic molecules. CNTs can be internalized by cells via endocytosis, passive diffusion and phagocytosis and release the drug with different effects like pH and temperature. The acidic nature of cancer cells and the susceptibility of CNTs to release the drug in the acidic environment have made it a promising area of research in cancer drug delivery. In this research, we investigated cell viability, cytotoxicity and drug delivery in breast cancer cell line by designing non-covalent single walled carbon nanotubes (SWNT)-doxorubicin (DOX) supramolecular complex that can be developed for cancer therapy. Applied high concentrations of DOX loaded SWNTs changed the actin structure of the cells and prevented the proliferation of the cells. It was showed that doxorubicin loaded SWNTs were more effective than free doxorubicin at relatively small concentrations. Once we applied same procedure for short and long (short: 1-1.3 µm; long: 2.5-4 µm) SWNTs and compared the results, more disrupted cell structure and reduction in cell proliferation were observed for long CNTs. DOX is bounded more to nanotubes in basic medium, less bound in acidic environment. Cancer cells were also examined for concentration at which they were effective by applying DOX and it was seen that 3.68 µM doxorubicin kills more than 55% of the cells.

摘要

碳纳米管(CNTs)是高效药物递送的一种新选择,在改变制药行业药物递送系统方面具有巨大潜力。碳纳米管的一个重要优势是其针状的圆柱形形状。这种形状为数百万个治疗分子的多重连接和吸附提供了高表面积。碳纳米管可通过内吞作用、被动扩散和吞噬作用被细胞内化,并在不同条件如pH值和温度下释放具有不同效果的药物。癌细胞的酸性性质以及碳纳米管在酸性环境中释放药物的敏感性使其成为癌症药物递送领域一个有前景的研究方向。在本研究中,我们通过设计可用于癌症治疗的非共价单壁碳纳米管(SWNT)-阿霉素(DOX)超分子复合物,研究了乳腺癌细胞系中的细胞活力、细胞毒性和药物递送情况。应用高浓度负载阿霉素的碳纳米管改变了细胞的肌动蛋白结构并阻止了细胞增殖。结果表明,在相对较低浓度下,负载阿霉素的碳纳米管比游离阿霉素更有效。一旦我们对短(1-1.3微米)和长(2.5-4微米)碳纳米管应用相同程序并比较结果,发现长碳纳米管对细胞结构的破坏更大,细胞增殖减少更多。阿霉素在碱性介质中与纳米管的结合更多,在酸性环境中结合较少。还通过应用阿霉素检测了癌细胞有效的浓度,发现3.68微摩尔的阿霉素可杀死超过55%的细胞。

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