Insight of Synergistic Effect between CPP and Cargo on the Facilitation Mechanisms of R7-PTX Translocation: Experiments and Molecular Simulations | |
Wei, Yuping2,5; Zhang, Caiying2; Zhang, Man2,4; Niu, Qionghong2; Hui, Fengli2; Liu, Zi1,3; Xu, Xia1,3,5 | |
刊名 | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES |
2021-06-01 | |
卷号 | 161页码:9 |
关键词 | Cell penetrating peptide Molecular dynamic simulation Synergistic effect Direct translocation Endocytosis |
ISSN号 | 0928-0987 |
DOI | 10.1016/j.ejps.2021.105790 |
英文摘要 | In our previous study, a novel cell penetrating peptide (CPP) R7 (Arg-Arg-Arg-Arg-Arg-Trp-Trp, RRRRRWW) has been developed to help cellular internalization of paclitaxel (PTX) through the non-covalent interaction with CPP. However, the facilitation mechanism of R7 mediated PTX translocation is not clear. Here the uptake pathways of R7 and R7-PTX were investigated by in vitro test and molecular simulations. In vitro experiments reveal that both R7 and R7-PTX complex translocate through the direct translocation and clathrin mediated endocytosis and associate with the macropinocytosis pathway at high CPP concentration. The translocation of R7 (0.1 mM)-PTX complex further involves the lipid raft/caveolae mediated endocytosis. The simulation results show that the synergistic effect between R7 and PTX not only changes the penetration energy barrier but also activates the macropinocytosis and lipid raft/caveolae mediated pathway, resulting in the improvement in the translocation. The presence of heparin also improves the R7 and R7-PTX translocation. These studies provide a theoretical basis for understanding PTX delivery facilitated by the synergistic effect between CPP and cargo and paves a way for CPP design. |
资助项目 | National Natural Science Foundation of China[21506230] ; National Natural Science Foundation of China[21978001] ; National Natural Science Foundation of China[31770138] ; National Natural Science Foundation of China[31570120] ; Wanjiang Scholar Program from Anhui University of Technology ; Start Fund for Biochemical Engineering Research Center from Anhui University of Technology ; Scientific and Technological Project of Henan Province[202102310537] ; Schoollevel Research Project of Nanyang Normal University[2019ZX012] |
WOS关键词 | CELL-PENETRATING PEPTIDES ; ARGININE-RICH PEPTIDES ; DELIVERY ; INTERNALIZATION ; ENDOCYTOSIS ; PACLITAXEL ; MEMBRANES ; KINETICS ; DOCKING ; HEPARIN |
WOS研究方向 | Pharmacology & Pharmacy |
语种 | 英语 |
出版者 | ELSEVIER |
WOS记录号 | WOS:000640914000002 |
资助机构 | National Natural Science Foundation of China ; Wanjiang Scholar Program from Anhui University of Technology ; Start Fund for Biochemical Engineering Research Center from Anhui University of Technology ; Scientific and Technological Project of Henan Province ; Schoollevel Research Project of Nanyang Normal University |
内容类型 | 期刊论文 |
源URL | [http://ir.ipe.ac.cn/handle/122111/48596] |
专题 | 中国科学院过程工程研究所 |
通讯作者 | Xu, Xia |
作者单位 | 1.Anhui Univ Technol, Dept Chem Biol, Sch Chem & Chem Engn, Maanshan 243032, Anhui, Peoples R China 2.Nanyang Normal Univ, Sch Life Sci & Agr Engn, Nanyang 473061, Henan, Peoples R China 3.Anhui Univ Technol, Biochem Engn Res Ctr, Maanshan 243032, Anhui, Peoples R China 4.Nanyang First Peoples Hosp, Dept Oncol, Nanyang 473002, Henan, Peoples R China 5.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China |
推荐引用方式 GB/T 7714 | Wei, Yuping,Zhang, Caiying,Zhang, Man,et al. Insight of Synergistic Effect between CPP and Cargo on the Facilitation Mechanisms of R7-PTX Translocation: Experiments and Molecular Simulations[J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,2021,161:9. |
APA | Wei, Yuping.,Zhang, Caiying.,Zhang, Man.,Niu, Qionghong.,Hui, Fengli.,...&Xu, Xia.(2021).Insight of Synergistic Effect between CPP and Cargo on the Facilitation Mechanisms of R7-PTX Translocation: Experiments and Molecular Simulations.EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,161,9. |
MLA | Wei, Yuping,et al."Insight of Synergistic Effect between CPP and Cargo on the Facilitation Mechanisms of R7-PTX Translocation: Experiments and Molecular Simulations".EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 161(2021):9. |
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