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Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA delivery
Gao, Ling-Yan; Liu, Xiao-Yan; Chen, Cheng-Jun; Wang, Jian-Cheng; Feng, Qiang; Yu, Min-Zhi; Ma, Xiao-Fei; Pei, Xi-Wei; Niu, Yu-Jie; Qiu, Chong; Pang, Wen-Hao; Zhang, Qiang
关键词Core-shell Hybrid Nanoparticle Sirna Delivery Receptor-mediated Targeting Tumor Therapy
刊名BIOMATERIALS
2014-02-01
DOI10.1016/j.biomaterials.2013.11.046
35期:6页:2066-2078
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]GENE DELIVERY ; TERNARY COMPLEXES ; TRANSFERRIN RECEPTOR ; TARGETED DELIVERY ; CRYO-TEM ; ENDOCYTOSIS ; CANCER ; DNA ; TRANSFECTION ; THERAPY
英文摘要

Our previous study had reported that cholesterol-grafted poly(amidoamine) (rPAA-Chol polymer) was able to self-assemble into cationic nanoparticles and act as a potential carrier for siRNA transfection. In this study, the core shell type lipid/rPAA-Chol hybrid nanoparticles (PEG-LP/siRNA NPs and T7-LP/siRNA NPs) were developed for improving in vivo siRNA delivery by modifying the surface of rPAA-Chol/siRNA nanoplex core with a lipid shell, followed by post-insertion of polyethylene glycol phospholipid (DSPE-PEG) and/or peptide (HAIYPRH, named as T7) modified DSPE-PEG-T7. The integrative hybrid nanostructures of LP/siRNA NPs were evidenced by dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), cryo-transmission electron microscope (Cryo-TEM) and surface plasmon resonance (SPR) assay. It was demonstrated that the T7 peptide modified LP/siRNA NPs (T7-LP/siRNA NPs) exhibited uniform and spherical structures with particle size of 99.39 +/- 0.65 nm and surface potential of 42.53 +/- 1.03 my, and showed high cellular uptake efficiency and rapid endosomal/lysosomal escape ability in MCF-7 cells. Importantly, in vitro gene silencing experiment demonstrated that both of pegylated and targeted LP/siEGFR NPs exhibited significantly stronger downregulation of EGFR protein expression level in MCF-7 cells, compared to that of the physical mixture of siRNA lipoplexes and rPAA-Chol/siRNA nanoplexes. In vivo tumor therapy on nude mice bearing MCF-7 tumors further confirmed that the targeted T7-LP/siEGFR NPs exhibited the greatest inhibition on tumor growth via transferrin receptor-mediated targeting delivery, without any activation of immune responses and significant body weight loss following systemic administration. These findings indicated that the core-shell type T7-LP/siRNA nanopartides would be promising siRNA delivery systems for in vivo tumor-targeted therapy. (C) 2013 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000331018700028
项目编号81273455 ; 81072597 ; 2013CB932501 ; 7112089 ; NCET-11-0014 ; BMU20110263
资助机构NSFC ; National 973 Program of China ; Beijing NSF project ; Ministry of Education ; State Key Laboratory of Long-acting and Targeting Drug Delivery System, LUYE PHARMA
引用统计
被引频次:35[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56645
专题北京大学药学院
北京大学药学院_药剂学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Gao, Ling-Yan,Liu, Xiao-Yan,Chen, Cheng-Jun,et al. Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA delivery[J]. BIOMATERIALS,2014,35(6):2066-2078.
APA Gao, Ling-Yan.,Liu, Xiao-Yan.,Chen, Cheng-Jun.,Wang, Jian-Cheng.,Feng, Qiang.,...&Zhang, Qiang.(2014).Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA delivery.BIOMATERIALS,35(6),2066-2078.
MLA Gao, Ling-Yan,et al."Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA delivery".BIOMATERIALS 35.6(2014):2066-2078.
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