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SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment
Alternative TitleBiomaterials
Liu, Hongmei1,2; Li, Yan1,2; Mozhi, Anbu3; Zhang, Liang1,2; Liu, Yilan1,2; Xu, Xia1; Xing, Jianmin1; Liang, Xingjie3; Ma, Guanghui1; Yang, Jun1; Zhang, Xin1
2014-08-01
Source PublicationBIOMATERIALS
ISSN0142-9612
Volume35Issue:24Pages:6519-6533
AbstractDue to low charge density and stiff backbone structure, small interfering RNA (siRNA) has inherently poor binding ability to cationic polymers and lipid carriers, which results in low siRNA loading efficiency and limits siRNA success in clinical application. Here, siRNA-phospholipids conjugates are developed, which integrate the characteristics of the two phospholipids to self-assemble via hydrophilic siRNA and hydrophobic phospholipid tails to overcome the siRNA's stiff backbone structures and enhance the siRNA loading efficiency. In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs and hydrophobic anticancer drugs into tumor. In animal models, intravenously injected siRNA-PCNPs embedded DOX (siPlk1-PCNPs/DOX) is highly effective in inhibiting tumor growth. The results indicate that the siRNA-PCNPs can be potentially applied as a safe and efficient gene and anticancer drug delivery carrier. (C) 2014 Elsevier Ltd. All rights reserved.; Due to low charge density and stiff backbone structure, small interfering RNA (siRNA) has inherently poor binding ability to cationic polymers and lipid carriers, which results in low siRNA loading efficiency and limits siRNA success in clinical application. Here, siRNA-phospholipids conjugates are developed, which integrate the characteristics of the two phospholipids to self-assemble via hydrophilic siRNA and hydrophobic phospholipid tails to overcome the siRNA's stiff backbone structures and enhance the siRNA loading efficiency. In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs and hydrophobic anticancer drugs into tumor. In animal models, intravenously injected siRNA-PCNPs embedded DOX (siPlk1-PCNPs/DOX) is highly effective in inhibiting tumor growth. The results indicate that the siRNA-PCNPs can be potentially applied as a safe and efficient gene and anticancer drug delivery carrier. (C) 2014 Elsevier Ltd. All rights reserved.
KeywordCombined Effect Sirna-phospholipids Conjugate Gene Silencing Loading Efficiency
SubtypeArticle
WOS HeadingsScience & Technology ; Technology
DOI10.1016/j.biomaterials.2014.04.033
URL查看原文
Indexed BySCI
Language英语
WOS KeywordPOLO-LIKE KINASES ; CO-DELIVERY ; HYBRID NANOPARTICLES ; EFFICIENT ; POLYMER ; DOXORUBICIN ; MICELLES ; TRANSFECTION ; NANOCARRIERS ; CHEMOTHERAPY
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, Biomaterials
WOS IDWOS:000338804500036
Citation statistics
Cited Times:46[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/10936
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.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
Recommended Citation
GB/T 7714
Liu, Hongmei,Li, Yan,Mozhi, Anbu,et al. SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment[J]. BIOMATERIALS,2014,35(24):6519-6533.
APA Liu, Hongmei.,Li, Yan.,Mozhi, Anbu.,Zhang, Liang.,Liu, Yilan.,...&Zhang, Xin.(2014).SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment.BIOMATERIALS,35(24),6519-6533.
MLA Liu, Hongmei,et al."SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment".BIOMATERIALS 35.24(2014):6519-6533.
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