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SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment | |
Alternative Title | Biomaterials |
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 Publication | BIOMATERIALS
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ISSN | 0142-9612 |
Volume | 35Issue:24Pages:6519-6533 |
Abstract | 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.; 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. |
Keyword | Combined Effect Sirna-phospholipids Conjugate Gene Silencing Loading Efficiency |
Subtype | Article |
WOS Headings | Science & Technology ; Technology |
DOI | 10.1016/j.biomaterials.2014.04.033 |
URL | 查看原文 |
Indexed By | SCI |
Language | 英语 |
WOS Keyword | POLO-LIKE KINASES ; CO-DELIVERY ; HYBRID NANOPARTICLES ; EFFICIENT ; POLYMER ; DOXORUBICIN ; MICELLES ; TRANSFECTION ; NANOCARRIERS ; CHEMOTHERAPY |
WOS Research Area | Engineering ; Materials Science |
WOS Subject | Engineering, Biomedical ; Materials Science, Biomaterials |
WOS ID | WOS:000338804500036 |
Citation statistics | |
Document Type | 期刊论文 |
Version | 出版稿 |
Identifier | http://ir.ipe.ac.cn/handle/122111/10936 |
Collection | 研究所(批量导入) |
Affiliation | 1.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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