CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-<italic style="font-style: italic">b</italic>-PCL-<italic style="font-style: italic">b</italic>-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA

Ruo-gu Qi; Su-hong Wu; Yu Wang; Jie Chen; Zhi-gang Xie; Yu-bin Huang; Xia-bin Jing

doi:10.1007/s10118-013-1288-6

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CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA

Special Issue: In Honor of the 80th Birthday of Professor Fosong Wang (Part II) | Updated：2023-01-03

- CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA
- CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA
- Chinese Journal of Polymer Science 2013年31卷第6期页码：912-923
- Affiliations：
  
  a.State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
  b.University of Chinese Academy of Sciences, Beijing 100049, China
- Author bio：
  
  **Xia-bin Jing (景遐斌), E-mail: xbjing@ciac.jl.cn
- Funds：
  
  National Natural Science Foundation of China(21004062);"100 Talents Program" of the Chinese Academy of Sciences(KGCX2-YW-802);Ministry of Science and Technology of China(2009CB930102)
- DOI：10.1007/s10118-013-1288-6
  中图分类号：
- 收稿：2013-01-04，
  
  修回：2013-02-06，
  
  录用：2013-02-18，
  
  纸质出版：2013-06
- Accepted：
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Ruo-gu Qi, Su-hong Wu, Yu Wang, 等. CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA[J]. Chinese Journal of Polymer Science, 2013,31(6):912-923. DOI: 10.1007/s10118-013-1288-6.

Ruo-gu Qi, Su-hong Wu, Yu Wang, et al. CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA[J]. Chinese Journal of Polymer Science, 2013, 31(6): 912-923. DOI: 10.1007/s10118-013-1288-6.
Ruo-gu Qi, Su-hong Wu, Yu Wang, 等. CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA[J]. Chinese Journal of Polymer Science, 2013,31(6):912-923. DOI: 10.1007/s10118-013-1288-6. DOI：

Ruo-gu Qi, Su-hong Wu, Yu Wang, et al. CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA[J]. Chinese Journal of Polymer Science, 2013, 31(6): 912-923. DOI: 10.1007/s10118-013-1288-6. DOI：

摘要

Abstract

To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly(ethylene glycol)-

block

-poly(

-caprolactone)-

block

-poly(L-lysine) (MPEG-

-PCL-

-PLL)

cholesterol (Chol) moieties are attached to the

-termini of PLL segments to obtain MPEG-

-PCL-

-PLL/Chol. The structure and morphology of the copolymer are studied by

H-NMR

TEM and DLS (dynamic light scattering). The cytotoxicity

cell uptake

endosomal release and mRNA knockdown are studied by MTT (3-[4

5-dimethylthiazol-2-yl]-2

5-diphenyltetrazolium bromide) assay

flow cytometry

CLSM (confocal laser scanning microscopy) and RT-PCR (real-time polymerase chain reaction). The results show that compared to their precursor MPEG-

-PCL-

-PLL

the cholesterol-grafted copolymer shows significantly lower toxicity

more rapid cellular endocytosis and endosome escape

and consequently displays enhanced siRNA transfection efficiency even at a lower N/P ratio. These improvements are ascribed to enhanced interaction of the cholesterol moieties with both cellular membrane and endosomal membrane. Moreover

effect of the PLL block length is examined. The final conclusion is that long enough PLL segments and incorporation of proper fraction of cholesterol onto the PLL segments benefit the enhancement of siRNA transfection efficiency.

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CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA

CONTRIBUTION OF CHOLESTEROL MOIETIES ATTACHED ON MPEG-b-PCL-b-PLL TO THE CELL UPTAKE, ENDOSOMAL ESCAPE AND GENE KNOCKDOWN OF THE MICELLEPLEXES OF siRNA

DOI：10.1007/s10118-013-1288-6

摘要

Abstract

关键词

Keywords

references