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Transferrin-PEG-PE modified dexamethasone conjugated cationic lipid carrier mediated gene delivery system for tumor-targeted transfection.

Wang W, Zhou F, Ge L, Liu X, Kong F - Int J Nanomedicine (2012)

Bottom Line: As such, the aim of this study was to develop a type of vector that can target cells through receptor-mediated pathways and by using nuclear localization signal (NLS) to increase the nuclear uptake of genetic materials.A dexamethasone (Dexa)-conjugated lipid was synthesized as the material of the solid lipid nanoparticles (SLNs), and transferrin (Tf) was linked onto polyethylene glycol-phosphatidylethanolamine (PEG-PE) to obtain Tf-PEG-PE ligands for the surface modification of the carriers.Tf-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) had a particle size of 222 nm and a gene loading quantity of 90%.

View Article: PubMed Central - PubMed

Affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji'nan Command, Ji'nan, China.

ABSTRACT

Background: The main barriers to non-viral gene delivery include cellular and nuclear membranes. As such, the aim of this study was to develop a type of vector that can target cells through receptor-mediated pathways and by using nuclear localization signal (NLS) to increase the nuclear uptake of genetic materials.

Methods: A dexamethasone (Dexa)-conjugated lipid was synthesized as the material of the solid lipid nanoparticles (SLNs), and transferrin (Tf) was linked onto polyethylene glycol-phosphatidylethanolamine (PEG-PE) to obtain Tf-PEG-PE ligands for the surface modification of the carriers. The in vitro transfection efficiency of the novel modified vectors was evaluated in human hepatoma carcinoma cell lines, and in vivo effects were observed in an animal model.

Results: Tf-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) had a particle size of 222 nm and a gene loading quantity of 90%. Tf-PEG-PE-modified SLNs/pEGFP (Tf-SLNs/pEGFP) displayed remarkably higher transfection efficiency than non-modified SLNs/pEGFP and the vectors not containing Dexa, both in vitro and in vivo.

Conclusion: It can be concluded that Tf and Dexa could function as an excellent active targeting ligand to improve the cell targeting and nuclear targeting ability of the carriers, and the resulting nanomedicine could be a promising active targeting drug/gene delivery system.

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Quantitation of in vivo transfection efficiencies of Tf-SLNs/pEGFP and other vectors at 24, 48, and 72 hours post-transfection. Abbreviations: Tf, transferrin; SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Dexa, dexamethasone.
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f10-ijn-7-2513: Quantitation of in vivo transfection efficiencies of Tf-SLNs/pEGFP and other vectors at 24, 48, and 72 hours post-transfection. Abbreviations: Tf, transferrin; SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Dexa, dexamethasone.

Mentions: In vivo gene delivery activity of Tf-SLNs/pEGFP was evaluated against HepG2 solid tumors in mice. The in vivo transfection efficiencies of Tf-SLNs/pEGFP, naked DNA, unmodified SLNs/pEGFP, non-Dexa-SLNs/pEGFP, and Tf-non- Dexa-SLNs/pEGFP were observed and are shown in Figure 9. Tf-SLNs/pEGFP had a higher transfection efficiency at different time intervals than the other vectors. Flow cytometry was applied to future quantitate the cells that were successfully transfected. As shown in Figure 10, Tf-SLNs/pEGFP displayed remarkably higher transfection efficiency than SLNs/pEGFP and the other vectors (P < 0.05).


Transferrin-PEG-PE modified dexamethasone conjugated cationic lipid carrier mediated gene delivery system for tumor-targeted transfection.

Wang W, Zhou F, Ge L, Liu X, Kong F - Int J Nanomedicine (2012)

Quantitation of in vivo transfection efficiencies of Tf-SLNs/pEGFP and other vectors at 24, 48, and 72 hours post-transfection. Abbreviations: Tf, transferrin; SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Dexa, dexamethasone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367492&req=5

f10-ijn-7-2513: Quantitation of in vivo transfection efficiencies of Tf-SLNs/pEGFP and other vectors at 24, 48, and 72 hours post-transfection. Abbreviations: Tf, transferrin; SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Dexa, dexamethasone.
Mentions: In vivo gene delivery activity of Tf-SLNs/pEGFP was evaluated against HepG2 solid tumors in mice. The in vivo transfection efficiencies of Tf-SLNs/pEGFP, naked DNA, unmodified SLNs/pEGFP, non-Dexa-SLNs/pEGFP, and Tf-non- Dexa-SLNs/pEGFP were observed and are shown in Figure 9. Tf-SLNs/pEGFP had a higher transfection efficiency at different time intervals than the other vectors. Flow cytometry was applied to future quantitate the cells that were successfully transfected. As shown in Figure 10, Tf-SLNs/pEGFP displayed remarkably higher transfection efficiency than SLNs/pEGFP and the other vectors (P < 0.05).

Bottom Line: As such, the aim of this study was to develop a type of vector that can target cells through receptor-mediated pathways and by using nuclear localization signal (NLS) to increase the nuclear uptake of genetic materials.A dexamethasone (Dexa)-conjugated lipid was synthesized as the material of the solid lipid nanoparticles (SLNs), and transferrin (Tf) was linked onto polyethylene glycol-phosphatidylethanolamine (PEG-PE) to obtain Tf-PEG-PE ligands for the surface modification of the carriers.Tf-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) had a particle size of 222 nm and a gene loading quantity of 90%.

View Article: PubMed Central - PubMed

Affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji'nan Command, Ji'nan, China.

ABSTRACT

Background: The main barriers to non-viral gene delivery include cellular and nuclear membranes. As such, the aim of this study was to develop a type of vector that can target cells through receptor-mediated pathways and by using nuclear localization signal (NLS) to increase the nuclear uptake of genetic materials.

Methods: A dexamethasone (Dexa)-conjugated lipid was synthesized as the material of the solid lipid nanoparticles (SLNs), and transferrin (Tf) was linked onto polyethylene glycol-phosphatidylethanolamine (PEG-PE) to obtain Tf-PEG-PE ligands for the surface modification of the carriers. The in vitro transfection efficiency of the novel modified vectors was evaluated in human hepatoma carcinoma cell lines, and in vivo effects were observed in an animal model.

Results: Tf-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) had a particle size of 222 nm and a gene loading quantity of 90%. Tf-PEG-PE-modified SLNs/pEGFP (Tf-SLNs/pEGFP) displayed remarkably higher transfection efficiency than non-modified SLNs/pEGFP and the vectors not containing Dexa, both in vitro and in vivo.

Conclusion: It can be concluded that Tf and Dexa could function as an excellent active targeting ligand to improve the cell targeting and nuclear targeting ability of the carriers, and the resulting nanomedicine could be a promising active targeting drug/gene delivery system.

Show MeSH
Related in: MedlinePlus