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小麦胚凝集素修饰的磁性氧化铁纳米复合物作为一种用于杀伤乳腺癌细胞的细胞膜特异性受体靶向材料。

Wheat germ agglutinin modified magnetic iron oxide nanocomplex as a cell membrane specific receptor target material for killing breast cancer cells.

作者信息

Upadhyay Aekta, Kandi Ravinder, Rao Chebrolu Pulla

机构信息

Bioinorganic Laboratory, Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400 076, India.

出版信息

J Mater Chem B. 2018 Sep 28;6(36):5729-5737. doi: 10.1039/c8tb01170b. Epub 2018 Aug 24.

Abstract

Lectins are known for their specificity for carbohydrate binding. However, a few specific carbohydrate residues are over expressed in cancer cells, which may be an advantage for using a lectin that is specific to such residues. Herein, we report the strategic design of wheat germ agglutinin (WGA) and a fluorescent torch, FITC immobilized on FeO NPs as a cell membrane specific receptor target for breast cancer cells, viz., MCF-7 and MDA-MB-231. The resultant nanocomplexes were well characterized by using microscopy and spectroscopy. The WGA tagged nanocomplex was further loaded with the anticancer drug 5-fluorouracil (5-FU) to selectively kill the cancer cells. The loading efficiency of 5-FU is ∼356 μg mg. The nanocomplex itself shows ∼90% cell viability for all the four cell lines (HEK, HeLa, MCF-7 and MDA-MB-231) studied and is therefore a suitable targeting drug delivery vehicle. However, the nanocomplex loaded with {WGA + 5-FU} shows a ∼1.5-fold decrease in cell viability in the case of specific cells (MCF-7 and MDA-MB-231) when compared to non-specific cells (HeLa and HEK). The internalization of the nanocomplex is supported by fluorescence microscopy and confocal laser scanning microscopy techniques by tracking with the fluorescent torch, FITC. The nanocomplex can be internalized ∼2 times more in the specific cells as compared to the non-specific cells. It is observed that the internalization is ∼2 fold increased when the MDA-MB-231 cells are exposed to a magnetic field for 24 h as compared to in the absence of a magnetic field. Live-dead cell assay of the 5-FU loaded nanocomplex was done by propidium iodide (PI) staining. There is an increase in the cell death by ∼2.5 fold when the cells are under a magnetic field as measured from the PI uptake. Such strategic designing of the nanocomplex can lead to the development of a better method to selectively target and kill the cancer cells by acting as a carrier to deliver a suitable drug, as a result of which the medical field can benefit.

摘要

凝集素以其对碳水化合物结合的特异性而闻名。然而,一些特定的碳水化合物残基在癌细胞中过度表达,这对于使用对这些残基具有特异性的凝集素来说可能是一个优势。在此,我们报告了小麦胚芽凝集素(WGA)和一种荧光标记物异硫氰酸荧光素(FITC)固定在FeO纳米颗粒上作为乳腺癌细胞(即MCF-7和MDA-MB-231)细胞膜特异性受体靶点的策略性设计。使用显微镜和光谱学对所得纳米复合物进行了充分表征。用WGA标记的纳米复合物进一步负载抗癌药物5-氟尿嘧啶(5-FU)以选择性杀死癌细胞。5-FU的负载效率约为356μg/mg。纳米复合物本身对所研究的所有四种细胞系(HEK、HeLa、MCF-7和MDA-MB-231)显示出约90%的细胞活力,因此是一种合适的靶向药物递送载体。然而,与非特异性细胞(HeLa和HEK)相比,负载{WGA + 5-FU}的纳米复合物在特定细胞(MCF-7和MDA-MB-231)中的细胞活力降低了约1.5倍。通过用荧光标记物FITC追踪,荧光显微镜和共聚焦激光扫描显微镜技术证实了纳米复合物的内化。与非特异性细胞相比,纳米复合物在特定细胞中的内化量可多约2倍。据观察,与无磁场时相比,当MDA-MB-231细胞暴露于磁场24小时时,内化增加了约2倍。通过碘化丙啶(PI)染色对负载5-FU的纳米复合物进行活死细胞测定。从PI摄取量测量,当细胞处于磁场中时,细胞死亡增加了约2.5倍。这种纳米复合物的策略性设计可以导致开发一种更好的方法,通过作为载体递送合适的药物来选择性地靶向和杀死癌细胞,从而使医学领域受益。

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