PubAg

Main content area

Enhanced gene transfection efficiency in CD13-positive vascular endothelial cells with targeted poly(lactic acid)–poly(ethylene glycol) nanoparticles through caveolae-mediated endocytosis

Author:
Liu, Chunxi, Yu, Wangyang, Chen, Zhijin, Zhang, Jian, Zhang, Na
Source:
Journal of controlled release 2011 v.151 no.2 pp. 162-175
ISSN:
0168-3659
Subject:
DNA, biocompatibility, cationic surfactants, cytotoxicity, endocytosis, endothelial cells, genes, nanoparticles, transfection
Abstract:
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 (<200nm) with positive charge (~10mV). 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.
Agid:
1009854