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]
  Changlin Su , Wensheng Cai , Xueguang Shao . Water as a probe for the temperature-induced self-assembly transition of an amphiphilic copolymer. Chinese Chemical Letters, 2025, 36(4): 110095-. doi: 10.1016/j.cclet.2024.110095
2. [2]
  Liqing Chen , Zheming Zhang , Yanhong Liu , Chenfei Liu , Congcong Xiao , Liming Gong , Mingji Jin , Zhonggao Gao , Wei Huang . Systemically intravenous siRNA delivery into brain with a targeting and efficient polypeptide carrier and its evaluation on anti-glioma efficacy. Chinese Chemical Letters, 2025, 36(3): 110228-. doi: 10.1016/j.cclet.2024.110228
3. [3]
  Xingqun Pu , Rongrong Liu , Yuting Xie , Chenjing Yang , Jingyi Chen , Baoling Guo , Chun-Xia Zhao , Peng Zhao , Jian Ruan , Fangfu Ye , David A Weitz , Dong Chen . One-step preparation of biocompatible amphiphilic dimer nanoparticles with tunable particle morphology and surface property for interface stabilization and drug delivery. Chinese Chemical Letters, 2025, 36(3): 109820-. doi: 10.1016/j.cclet.2024.109820
4. [4]
  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
5. [5]
  Yunjie Dang , Yanru Feng , Xiao Chen , Chaoxing He , Shujie Wei , Dingyang Liu , Jinlong Qi , Huaxing Zhang , Shaokun Yang , Zhiyun Niu , Bai Xiang . Development of a multi-level pH-responsive lipid nanoplatform for efficient co-delivery of siRNA and small-molecule drugs in tumor treatment. Chinese Chemical Letters, 2024, 35(12): 109660-. doi: 10.1016/j.cclet.2024.109660
6. [6]
  Makhloufi Zoulikha , Zhongjian Chen , Jun Wu , Wei He . Approved delivery strategies for biopharmaceuticals. Chinese Chemical Letters, 2025, 36(2): 110225-. doi: 10.1016/j.cclet.2024.110225
7. [7]
  Dongpu Wu , Zheng Yang , Yuchen Xia , Lulu Wu , Yingxia Zhou , Caoyuan Niu , Puhui Xie , Xin Zheng , Zhanqi Cao . Surface controllable wettability using amphiphilic rotaxane molecular shuttles. Chinese Chemical Letters, 2025, 36(2): 110353-. doi: 10.1016/j.cclet.2024.110353
8. [8]
  Chong Liu , Ling Li , Jiahui Gao , Yanwei Li , Nazhen Zhang , Jing Zang , Cong Liu , Zhaopei Guo , Yanhui Li , Huayu Tian . The study of antibacterial activity of cationic poly(β-amino ester) regulating by amphiphilic balance. Chinese Chemical Letters, 2025, 36(2): 110118-. doi: 10.1016/j.cclet.2024.110118
9. [9]
  Yiwen Lin , Yijie Chen , Chunhui Deng , Nianrong Sun . Integration of resol/block-copolymer carbonization and machine learning: A convenient approach for precise monitoring of glycan-associated disorders. Chinese Chemical Letters, 2024, 35(12): 109813-. doi: 10.1016/j.cclet.2024.109813
10. [10]
  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
11. [11]
  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
12. [12]
  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
13. [13]
  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
14. [14]
  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
15. [15]
  Xueyan Zhang , Jicong Chen , Songren Han , Shiyan Dong , Huan Zhang , Yuhong Man , Jie Yang , Ye Bi , Lesheng Teng . The size-switchable microspheres co-loaded with RANK siRNA and salmon calcitonin for osteoporosis therapy. Chinese Chemical Letters, 2024, 35(12): 109668-. doi: 10.1016/j.cclet.2024.109668
16. [16]
  Kai Wang , Yun Wang , Lihang Wang , Zhuhai Li , Xi Yu , Xuanhe You , Diwei Wu , Yueming Song , Jiancheng Zeng , Zongke Zhou , Shishu Huang , Yunfeng Lin . Therapeutic siRNA targeting CC chemokine receptor 2 loaded with tetrahedral framework nucleic acid alleviates neuropathic pain by regulating microglial polarization. Chinese Chemical Letters, 2025, 36(3): 109868-. doi: 10.1016/j.cclet.2024.109868
17. [17]
  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
18. [18]
  Jing Zhang , Charles Wang , Yaoyao Zhang , Haining Xia , Yujuan Wang , Kun Ma , Junfeng Wang . Application of magnetotactic bacteria as engineering microrobots: Higher delivery efficiency of antitumor medicine. Chinese Chemical Letters, 2024, 35(10): 109420-. doi: 10.1016/j.cclet.2023.109420
19. [19]
  Yujie Li , Ya-Nan Wang , Yin-Gen Luo , Hongcai Yang , Jinrui Ren , Xiao Li . Advances in synthetic biology-based drug delivery systems for disease treatment. Chinese Chemical Letters, 2024, 35(11): 109576-. doi: 10.1016/j.cclet.2024.109576
20. [20]
  Weiyu Chen , Zenghui Li , Chenguang Zhao , Lisha Zha , Junfeng Shi , Dan Yuan . Enzyme-modulate conformational changes in amphiphile peptide for selectively cell delivery. Chinese Chemical Letters, 2024, 35(12): 109628-. doi: 10.1016/j.cclet.2024.109628

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