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生物可还原型聚乙烯亚胺作为非病毒载体在乳腺癌基因治疗中的 miRNA 递送

MicroRNA Delivery with Bioreducible Polyethylenimine as a Non-Viral Vector for Breast Cancer Gene Therapy.

机构信息

Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.

出版信息

Macromol Biosci. 2019 Apr;19(4):e1800445. doi: 10.1002/mabi.201800445. Epub 2019 Jan 6.

DOI:10.1002/mabi.201800445
PMID:30614181
Abstract

Polyethylenimines (PEIs) are outstanding macromolecules belonging to the polycations used in gene transfection. The transfection efficiency and cytotoxicity of PEIs increase with the increase in their molecular weight. To break up the correlation between transfection efficiency and cytotoxicity for non-viral gene delivery, disulfide cross-linked polyethylenimine (PEI-SS) has been widely employed as highly efficient gene vectors for DNA/siRNA delivery in numerous efforts. In this work, PEI-SS is described as a non-viral vector for miRNA delivery for the first time. PEI-SS is synthesized via cross-linking using disulfide bonds as the cross-linker from low molecular weight PEI. PEI-SS can efficiently bind anti-miR-155 to form the polyplex with nano-sized spherical structures in the size range of 10-100 nm. The polyplex is degraded by glutathione (GSH, a reducing agent) in cancer cells. Anti-miR-155 is then released to efficiently inhibit tumor growth.

摘要

聚亚乙基亚胺(PEI)是一种出色的高分子聚合物,属于用于基因转染的聚阳离子。PEI 的分子量增加,其转染效率和细胞毒性也随之增加。为了打破非病毒基因传递中转染效率和细胞毒性之间的相关性,已广泛采用二硫键交联聚亚乙基亚胺(PEI-SS)作为高效的 DNA/siRNA 传递基因载体。在这项工作中,PEI-SS 首次被描述为 miRNA 传递的非病毒载体。PEI-SS 是通过使用二硫键作为交联剂从低分子量 PEI 交联合成的。PEI-SS 可以有效地结合抗 miR-155,形成具有纳米级球形结构的聚集体,尺寸范围为 10-100nm。聚集体在癌细胞中被谷胱甘肽(GSH,一种还原剂)降解。然后释放抗 miR-155,以有效地抑制肿瘤生长。

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