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用于靶向基因传递至三阴性乳腺癌的低分子量聚乙烯亚胺共轭瓜尔胶

Low molecular weight polyethyleneimine conjugated guar gum for targeted gene delivery to triple negative breast cancer.

作者信息

Jana Piyali, Ghosh Santanu, Sarkar Kishor

机构信息

Gene Therapy and Tissue Engineering Lab, Department of Polymer Science and Technology, University of Calcutta, 92, A.P.C. Road, Kolkata 700009, India.

Gene Therapy and Tissue Engineering Lab, Department of Polymer Science and Technology, University of Calcutta, 92, A.P.C. Road, Kolkata 700009, India.

出版信息

Int J Biol Macromol. 2020 Oct 15;161:1149-1160. doi: 10.1016/j.ijbiomac.2020.06.090. Epub 2020 Jun 15.

Abstract

The study emphasized on the development of an efficient, receptor-targeted non-viral gene delivery vehicle for gene therapy of triple negative breast cancer (TNBC). Here, naturally abundant guar gum based non-viral carrier was developed through conjugating by low molecular weight polyethylenimine (LPEI) (GNP) using napthalic anhydride coupling agent and characterized them by FT-IR, H NMR, XRD and UV spectrophotometer. The carrier was found to be cytocompatible as revealed by MTT assay against MDA-MB-231 and HeLa cell lines and excellent blood compatibility till the concentration of 200 μg/ml. In addition to these, the carrier exhibited excellent gene binding capability and formed spherical shaped complexes. The carrier showed very high in vitro transfection efficiency in TNBC cell (MDA-MB-231) compared to lipofectamine 2000 (LF2k) which could be justified by its high buffering capacity. Therefore, GNP may be an attractive non-viral gene carrier for gene therapy of TNBC in future.

摘要

该研究着重于开发一种高效的、靶向受体的非病毒基因递送载体,用于三阴性乳腺癌(TNBC)的基因治疗。在此,通过使用萘酐偶联剂将低分子量聚乙烯亚胺(LPEI)与天然丰富的瓜尔胶结合,开发出基于瓜尔胶的非病毒载体(GNP),并通过傅里叶变换红外光谱(FT-IR)、核磁共振氢谱(H NMR)、X射线衍射(XRD)和紫外分光光度计对其进行表征。通过针对MDA-MB-231和HeLa细胞系的MTT试验表明,该载体具有细胞相容性,并且在浓度达到200μg/ml时具有优异的血液相容性。除此之外,该载体表现出优异的基因结合能力,并形成球形复合物。与脂质体2000(LF2k)相比,该载体在TNBC细胞(MDA-MB-231)中显示出非常高的体外转染效率,这可以通过其高缓冲能力来解释。因此,GNP未来可能是一种有吸引力的用于TNBC基因治疗的非病毒基因载体。

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