Efficient targeted pDNA/siRNA delivery with folate–low-molecular-weight polyethyleneimine–modified pullulan as non-viral carrier
Folate receptor (FR)-mediated gene/short interfering RNA (siRNA) targeting shows advantage for the delivery of gene/siRNA into specific FR-overexpressing cancer cells. In this study, the non-targeted gene vector P–PEI was synthesized by grafting low-molecular-weight (1kDa) branched polyethyleneimine...
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Veröffentlicht in: | Materials Science & Engineering C 2014-01, Vol.34, p.98-109 |
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Sprache: | eng |
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Zusammenfassung: | Folate receptor (FR)-mediated gene/short interfering RNA (siRNA) targeting shows advantage for the delivery of gene/siRNA into specific FR-overexpressing cancer cells. In this study, the non-targeted gene vector P–PEI was synthesized by grafting low-molecular-weight (1kDa) branched polyethyleneimine (PEI) to succinylated pullulan, and the targeted gene vector P–PEI–FA was synthesized by coupling the carboxyl of folate (FA) to the amino of PEI. Gel electrophoresis retardation assay demonstrated that both P–PEI and P–PEI–FA can efficiently wrap pDNA and siRNA with electrostatic interaction at N/P ratios higher than 1.56 and can protect pDNA from degradation by DNase I and serum. Compared with PEI/pDNA, P–PEI/pDNA and P–PEI–FA/pDNA showed lower cytotoxicity against different cells. Under serum-containing conditions, compared with Lipofamine 2000/DNA and Lipofamine2000/siRNA, P–PEI–FA/DNA at N/P ratio of 6.25 displayed higher gene transfection efficiency, whereas P–PEI–FA/siRNA at N/P ratio of 12.5 demonstrated better enhanced gene silencing effect. P–PEI–FA/siRNA can also deliver FAM-labeled siRNA to endosomes and escape. Moreover, the gene transfection and silencing effects of P–PEI–FA were higher than those of P–PEI, and were dependent on the dose of FA in FR+ HeLa cells. Thus, P–PEI-FA can assist DNA or siRNA targeting to FR-overexpressing cells, and the uptake pathway of P–PEI–FA/siRNA was FR-mediated endocytosis. These results indicate that P–PEI–FA is a potential candidate for safe and targeted gene delivery applications.
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•New gene delivery vector, folate–PEI–modified pullulan (P–PEI–FA), was synthesized.•It can efficiently wrap pDNA/siRNA at optimal N/P, help pDNA against degradation.•P–PEI–FA/pDNA showed lower cytotoxicity, displayed high gene transfection efficiency.•P–PEI–FA/siRNA at N/P ratio of 12.5 demonstrated enhanced gene silencing effect.•P–PEI–FA can assist DNA or siRNA targeting to FR-overexpressing cells. |
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ISSN: | 0928-4931 1873-0191 |
DOI: | 10.1016/j.msec.2013.08.035 |