Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA
文献类型：期刊论文
| 作者 | Li, Yan1,4; Cheng, Qiang2; Jiang, Qian2; Huang, Yuanyu2; Liu, Hongmei1,4; Zhao, Yuliang3; Cao, Weipeng3; Ma, Guanghui1; Dai, Fengying1; Liang, Xingjie3 |
| 刊名 | JOURNAL OF CONTROLLED RELEASE
 |
| 出版日期 | 2014-02-28 |
| 卷号 | 176期号:1页码:104-114 |
| 关键词 | siRNA delivery Cationic liposomes Polycarboxybetaine pH-sensitive Endosomal/lysosomal escape |
| ISSN号 | 0168-3659 |
| 其他题名 | J. Control. Release |
| 中文摘要 | Cationic liposome based siRNA delivery system has improved the efficiencies of siRNA. However, cationic liposomes are prone to be rapidly cleared by the reticuloendothelial system (RES). Although modification of cationic liposomes with polyethylene glycol (PEG) could prolong circulation lifetime, PEG significantly inhibits siRNA entrapment efficiency, cellular uptake and endosomal/lysosomal escape process, resulting in low gene silencing efficiency of siRNA. In this study, we report the synthesis of zwitterionic polycarboxybetaine (PCB) based distearoyl phosphoethanolamine-polycarboxybetaine (DSPE-PCB) lipid for cationic liposome modification. The DSPE-PCB20 cationic liposome/siRNA complexes (lipoplexes) show an excellent stability in serum medium. The siRNA encapsulation efficiency of DSPE-PCB20 lipoplexes could reach 92% at N/P ratio of 20/1, but only 73% for DSPE-PEG lipoplexes. The zeta potential of DSPE-PCB20 lipoplexes is 8.19 +/- 0.53 mV at pH 7.4, and increases to 24.6 +/- 0.87 mV when the pH value is decreased to 4.5, which promotes the endosomal/lysosomal escape of siRNA. The DSPE-PCB20 modification could enhance the silencing efficiency of siRNA by approximately 20% over the DSPE-PEG 2000 lipoplexes at the same N/P ratio in vitro. Furthermore, DSPE-PCB20 lipoplexes could efficiently mediate the down-regulation of Apolipoprotein B (ApoB) mRNA in the liver and consequently decrease the total cholesterol in the serum in vivo, suggesting therapeutic potentials for siRNA delivery in hypercholesterolemia-related diseases. (C) 2013 Elsevier B. V. All rights reserved. |
| 英文摘要 | Cationic liposome based siRNA delivery system has improved the efficiencies of siRNA. However, cationic liposomes are prone to be rapidly cleared by the reticuloendothelial system (RES). Although modification of cationic liposomes with polyethylene glycol (PEG) could prolong circulation lifetime, PEG significantly inhibits siRNA entrapment efficiency, cellular uptake and endosomal/lysosomal escape process, resulting in low gene silencing efficiency of siRNA. In this study, we report the synthesis of zwitterionic polycarboxybetaine (PCB) based distearoyl phosphoethanolamine-polycarboxybetaine (DSPE-PCB) lipid for cationic liposome modification. The DSPE-PCB20 cationic liposome/siRNA complexes (lipoplexes) show an excellent stability in serum medium. The siRNA encapsulation efficiency of DSPE-PCB20 lipoplexes could reach 92% at N/P ratio of 20/1, but only 73% for DSPE-PEG lipoplexes. The zeta potential of DSPE-PCB20 lipoplexes is 8.19 +/- 0.53 mV at pH 7.4, and increases to 24.6 +/- 0.87 mV when the pH value is decreased to 4.5, which promotes the endosomal/lysosomal escape of siRNA. The DSPE-PCB20 modification could enhance the silencing efficiency of siRNA by approximately 20% over the DSPE-PEG 2000 lipoplexes at the same N/P ratio in vitro. Furthermore, DSPE-PCB20 lipoplexes could efficiently mediate the down-regulation of Apolipoprotein B (ApoB) mRNA in the liver and consequently decrease the total cholesterol in the serum in vivo, suggesting therapeutic potentials for siRNA delivery in hypercholesterolemia-related diseases. (C) 2013 Elsevier B. V. All rights reserved. |
| WOS标题词 | Science & Technology ; Physical Sciences ; Life Sciences & Biomedicine |
| 类目[WOS] | Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| 研究领域[WOS] | Chemistry ; Pharmacology & Pharmacy |
| 关键词[WOS] | CATIONIC LIPOSOMES ; GENE DELIVERY ; ZWITTERIONIC POLYMER ; POLYETHYLENE-GLYCOL ; ENDOSOMAL ESCAPE ; CANCER-THERAPY ; DRUG-DELIVERY ; NUCLEIC-ACIDS ; IN-VITRO ; NANOPARTICLES |
| 收录类别 | SCI |
| 原文出处 | |
| 语种 | 英语 |
| WOS记录号 | WOS:000331815400011 |
| 公开日期 | 2014-05-06 |
| 版本 | 出版稿 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/8091]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Peking Univ, Inst Mol Med, Lab Nucle Acid Technol, Beijing 100871, Peoples R China 3.Chinese Acad Sci, Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yan,Cheng, Qiang,Jiang, Qian,et al. Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA[J]. JOURNAL OF CONTROLLED RELEASE,2014,176(1):104-114. |
| APA | Li, Yan.,Cheng, Qiang.,Jiang, Qian.,Huang, Yuanyu.,Liu, Hongmei.,...&Zhang, Xin.(2014).Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA.JOURNAL OF CONTROLLED RELEASE,176(1),104-114. |
| MLA | Li, Yan,et al."Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA".JOURNAL OF CONTROLLED RELEASE 176.1(2014):104-114. |
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来源：过程工程研究所
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