标题:Enhanced gene transfection efficiency in CD13-positive vascular endothelial cells with targeted poly(lactic acid)-poly(ethylene glycol) nanoparticles through caveolae-mediated endocytosis
作者:Liu, C.;Yu, W.;Chen, Z.;Zhang, J.;Zhang, N.
作者机构:[Liu, C] Department of Pharmaceutics, School of Pharmaceutical Science, Shandong University, 44 West Culture Road, Ji'nan 250012, China;[ Yu, W] Depar 更多
通讯作者:Zhang, N
通讯作者地址:[Zhang, N]Shandong Univ, Dept Pharmaceut, Sch Pharmaceut Sci, 44 W Culture Rd, Jinan 250012, Peoples R China.
来源:Journal of Controlled Release: Official Journal of the Controlled Release Society
出版年:2011
卷:151
期:2
页码:162-175
DOI:10.1016/j.jconrel.2011.02.027
关键词:Caveolae-mediated endocytosis;CD13;NGR;PLA-PEG nanoparticles;Targeted gene delivery
摘要:The efficient delivery of therapeutic gene into cells of interest is a critical challenge to broad application of non-viral vectors. The approach of introducing ligands that lead gene vectors to target caveolae-mediated endocytosis on nanoparticle surface might serve as a promising strategy for the effective gene transfection. Recently, in an attempt to enhance the possibility of caveolae-mediated endocytosis, we fabricated a peptide-targeted gene vector for highly efficient receptor-mediated intracellular delivery. Cyclic Asn-Gly-Arg (cNGR) peptide was used to target gene loaded poly(lactic acid)-poly(ethylene glycol) nanoparticles (PLA-PEG NPs) to HUVEC over-expressing CD13. Using 6-lauroxyhexyl lysinate (LHLN) as cationic surfactant, cNGR modified PLA-PEG NPs (cNGR-PEG-PLA NPs) were capable of complexing and compacting DNA into homogeneous small-sized complexes (< 200 nm) with positive charge (~ 10 mV). Fortunately, the results of in vitro cellular uptake tests and mechanism studies were consistent with our original hypothesis. The cNGR peptide presented on nanoparticles\' surface could specifically mediate the fast and efficient internalization of cNGR-PEG-PLA NPs into HUVEC. Moreover, free cNGR inhibited their intracellular uptake into HUVEC revealing the mechanism of receptor-mediated endocytosis. Furthermore, the inspiring results of the mechanism studies and transfection assays demonstrated that caveolae-mediated endocytosis was indeed mainly involved in the internalization of cNGR-PEG-PLA NPs into HUVEC and led to significant gene transfection efficiency in contrast with cNGR non-modified PLA-PEG NPs. Given such encouraging and favorable properties including biocompatibility, high transfer efficiency, low cytotoxicity, and fast uptake by nondestructive endocytic pathways, cNGR-PEG-PLA NPs could be a promising carrier for the intracellular delivery of therapeutic agents.
收录类别:EI;SCOPUS;SCIE
WOS核心被引频次:44
Scopus被引频次:47
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-79956160572&doi=10.1016%2fj.jconrel.2011.02.027&partnerID=40&md5=b2b59c0d0199eff4c9d5f7357d5d39ca
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