Citation: Ruo-gu Qi, Su-hong Wu, Yu Wang, Jie Chen, Zhi-gang Xie, Yu-bin Huang, Xia-bin Jing. 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 shu

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

Received Date: 4 January 2013
Revised Date: 6 February 2013

Fund Project: This work was financially supported by the National Natural Science Foundation of China (No. 21004062), 100 Talents Program of the Chinese Academy of Sciences (No. KGCX2-YW-802), and the Ministry of Science and Technology of China (973 Project, No. 2009CB930102).

To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly(ethylene glycol)-block-poly(-caprolactone)-block-poly(L-lysine) (MPEG-b-PCL-b-PLL), cholesterol (Chol) moieties are attached to the -termini of PLL segments to obtain MPEG-b-PCL-b-PLL/Chol. The structure and morphology of the copolymer are studied by 1H-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-b-PCL-b-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.
- Amphiphilic copolymer,
- Cholesterol,
- Endosome escape,
- Micelleplex,
- siRNA delivery
1. [1]
1. [1]
  Luyu Zhang , Zirong Dong , Shuai Yu , Guangyue Li , Weiwen Kong , Wenjuan Liu , Haisheng He , Yi Lu , Wei Wu , Jianping Qi . Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes (CLNs) for enhanced intranasal siRNA delivery. Chinese Chemical Letters, 2024, 35(7): 109101-. doi: 10.1016/j.cclet.2023.109101
2. [2]
  Junying Zhang , Ruochen Li , Haihua Wang , Wenbing Kang , Xing-Dong Xu . Photo-induced tunable luminescence from an aggregated amphiphilic ethylene-pyrene derivative in aqueous media. Chinese Chemical Letters, 2024, 35(6): 109216-. doi: 10.1016/j.cclet.2023.109216
3. [3]
  An Lu , Yuhao Guo , Yi Yan , Lin Zhai , Xiangyu Wang , Weiran Cao , Zijie Li , Zhixia Zhao , Yujie Shi , Yuanjun Zhu , Xiaoyan Liu , Huining He , Zhiyu Wang , Jian-Cheng Wang . Nanomedicine integrating the lipidic derivative of 5-fluorouracil, miriplatin and PD-L1 siRNA for enhancing tumor therapy. Chinese Chemical Letters, 2024, 35(6): 108928-. doi: 10.1016/j.cclet.2023.108928
4. [4]
  Qian Wang , Ting Gao , Xiwen Lu , Hangchao Wang , Minggui Xu , Longtao Ren , Zheng Chang , Wen Liu . Nanophase separated, grafted alternate copolymer styrene-maleic anhydride as an efficient room temperature solid state lithium ion conductor. Chinese Chemical Letters, 2024, 35(7): 108887-. doi: 10.1016/j.cclet.2023.108887
5. [5]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
6. [6]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
7. [7]
  Qin Yu , Haisheng He , Jianping Qi , Yi Lu , Wei Wu . Oral delivery of insulin by barbed microneedles actuated by intestinal peristalsis. Chinese Chemical Letters, 2024, 35(9): 109888-. doi: 10.1016/j.cclet.2024.109888
8. [8]
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9. [9]
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10. [10]
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11. [11]
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12. [12]
  Dexuan Xiao , Tianyu Chen , Tianxu Zhang , Sirong Shi , Mei Zhang , Xin Qin , Yunkun Liu , Longjiang Li , Yunfeng Lin . Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib. Chinese Chemical Letters, 2024, 35(4): 108602-. doi: 10.1016/j.cclet.2023.108602
13. [13]
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14. [14]
  Yi Cao , Xiaojiao Ge , Yuanyuan Wei , Lulu He , Aiguo Wu , Juan Li . Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition. Chinese Chemical Letters, 2024, 35(4): 108672-. doi: 10.1016/j.cclet.2023.108672
15. [15]
  Wenjia Wang , Xingyue He , Xiaojie Wang , Tiantian Zhao , Osamu Muraoka , Genzoh Tanabe , Weijia Xie , Tianjiao Zhou , Lei Xing , Qingri Jin , Hulin Jiang . Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin (Ⅳ) prodrug delivery and enhanced colorectal cancer therapy. Chinese Chemical Letters, 2024, 35(4): 108656-. doi: 10.1016/j.cclet.2023.108656
16. [16]
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