Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate

被引：18

作者：

Ye, Junxiao ^{[1
,2
]}

Pei, Xing ^{[1
]}

Cui, Hui ^{[1
]}

Yu, Zhili ^{[1
]}

Lee, Hyukjin ^{[3
]}

Wang, Jianxin ^{[4
]}

Wang, Xu ^{[1
]}

Sun, Lu ^{[1
]}

He, Huining ^{[1
]}

Yang, Victor C. ^{[1
,5
]}

机构：

[1] Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China

[2] Tsinghua Univ, Coll Pharm, Beijing 100084, Peoples R China

[3] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 13760, South Korea

[4] Fudan Univ, Sch Pharm, Dept Pharmaceut, Minist Educ,Key Lab Smart Drug Delivery, Shanghai, Peoples R China

[5] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY | 2018年 / 63卷

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

Cell penetrating peptide; siRNA delivery; Covalent CPP-siRNA chemical conjugate; Cell uptake mechanism; Cytotoxicity; MOLECULAR-WEIGHT PROTAMINE; PENETRATING PEPTIDES; DRUG-DELIVERY; NANOPARTICLES; VIVO; THERAPEUTICS; COMPLEXES; CELLS; TRANSDUCTION; EFFICIENT;

D O I：

10.1016/j.jiec.2018.02.005

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The covalent attachment of CPPs to siRNA molecules offers great potential for CPP-mediated siRNA delivery. We recently reported a concise and high-yield synthesis strategy of the cell-permeable, cytosol-dissociable LMWP-siRNA covalent conjugate. Herein, cell uptake mechanism and cellular toxicity studies of this conjugate were performed to evaluate the potential of LMWP-siRNA conjugate for clinical translation. Cellular uptake mechanism study indicated that the conjugate could be taken up by cells via multiple pathways, including direct penetration of the plasma membrane and clathrin- and caveolae-independent endocytosis. In vitro cytotoxicity study revealed that the conjugation promoted internalization in a low-toxic fashion. (C) 2018 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.

引用

页码：103 / 111

页数：9

共 34 条

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