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利用工程化脂蛋白复合物高效递送双 siRNA 和药物。

Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes.

机构信息

Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering , Brooklyn, New York 11201, United States.

Department of Biomedical Engineering, State University of New York Downstate Medical Center , Brooklyn, New York 11203, United States.

出版信息

Biomacromolecules. 2017 Sep 11;18(9):2688-2698. doi: 10.1021/acs.biomac.7b00203. Epub 2017 Aug 4.

Abstract

An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.

摘要

一种工程化的超charged 卷曲螺旋蛋白(CSP)和阳离子转染试剂 Lipofectamine 2000 结合在一起,形成脂蛋白复合物,用于双重递送 siRNA 和阿霉素。CSP 带有外部正电荷和轴向疏水性孔道,能够浓缩 siRNA 并包裹小分子化疗药物阿霉素。与 Lipofectamine 2000 相比,脂蛋白复合物显示出提高的阿霉素载药量。此外,它能够有效转染 MCF-7 乳腺癌细胞中的 GAPDH(60% 的敲低),效率与 Lipofectamine 2000 相当。当脂蛋白复合物负载阿霉素时,提高的阿霉素载药量(~40μg Dox/mg CSP)会导致 MCF-7 细胞活力显著下降。

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