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

Junxiao Ye; Xing Pei; Hui Cui; Zhili Yu; Hyukjin Lee; Jianxin Wang; Xu Wang; Lu Sun; Huining He; Victor C. Yang

doi:10.1016/j.jiec.2018.02.005

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

Junxiao Ye, Xing Pei, Hui Cui, Zhili Yu, Hyukjin Lee, Jianxin Wang, Xu Wang, Lu Sun, Huining He, Victor C. Yang

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	103-111
Number of pages	9
Journal	Journal of Industrial and Engineering Chemistry
Volume	63
DOIs	https://doi.org/10.1016/j.jiec.2018.02.005
State	Published - 25 Jul 2018

Bibliographical note

Publisher Copyright:
© 2018 The Korean Society of Industrial and Engineering Chemistry

Keywords

Cell penetrating peptide
Cell uptake mechanism
Covalent CPP-siRNA chemical conjugate
Cytotoxicity
siRNA delivery

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10.1016/j.jiec.2018.02.005

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title = "Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate",

abstract = "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.",

keywords = "Cell penetrating peptide, Cell uptake mechanism, Covalent CPP-siRNA chemical conjugate, Cytotoxicity, siRNA delivery",

author = "Junxiao Ye and Xing Pei and Hui Cui and Zhili Yu and Hyukjin Lee and Jianxin Wang and Xu Wang and Lu Sun and Huining He and Yang, {Victor C.}",

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T1 - Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate

AU - Ye, Junxiao

AU - Pei, Xing

AU - Cui, Hui

AU - Yu, Zhili

AU - Lee, Hyukjin

AU - Wang, Jianxin

AU - Wang, Xu

AU - Sun, Lu

AU - He, Huining

AU - Yang, Victor C.

PY - 2018/7/25

Y1 - 2018/7/25

N2 - 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.

AB - 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.

KW - Cell penetrating peptide

KW - Cell uptake mechanism

KW - Covalent CPP-siRNA chemical conjugate

KW - Cytotoxicity

KW - siRNA delivery

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DO - 10.1016/j.jiec.2018.02.005

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SN - 1226-086X

VL - 63

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EP - 111

JO - Journal of Industrial and Engineering Chemistry

JF - Journal of Industrial and Engineering Chemistry

ER -

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

Abstract

Bibliographical note

Keywords

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