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Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA
Alternative TitleJ. Control. Release
Li, Yan1,4; Cheng, Qiang2; Jiang, Qian2; Huang, Yuanyu2; Liu, Hongmei1,4; Zhao, Yuliang3; Cao, Weipeng3; Ma, Guanghui1; Dai, Fengying1; Liang, Xingjie3; Liang, Zicai2; Zhang, Xin1
2014-02-28
Source PublicationJOURNAL OF CONTROLLED RELEASE
ISSN0168-3659
Volume176Issue:1Pages:104-114
AbstractCationic 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.; 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.
KeywordSirna Delivery Cationic Liposomes Polycarboxybetaine Ph-sensitive Endosomal/lysosomal Escape
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences ; Life Sciences & Biomedicine
DOI10.1016/j.jconrel.2013.12.007
URL查看原文
Indexed BySCI
Language英语
WOS KeywordCATIONIC LIPOSOMES ; GENE DELIVERY ; ZWITTERIONIC POLYMER ; POLYETHYLENE-GLYCOL ; ENDOSOMAL ESCAPE ; CANCER-THERAPY ; DRUG-DELIVERY ; NUCLEIC-ACIDS ; IN-VITRO ; NANOPARTICLES
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:000331815400011
Citation statistics
Cited Times:56[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/8091
Collection研究所(批量导入)
Affiliation1.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
Recommended Citation
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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