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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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Preparation of Tf-PEG-PE-modified SLNs/pEGFP. Abbreviations: SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Tf, transferrin; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine.
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f3-ijn-7-2513: Preparation of Tf-PEG-PE-modified SLNs/pEGFP. Abbreviations: SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Tf, transferrin; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine.

Mentions: SLNs were prepared following the nanoprecipitation method (solvent displacement technique), as described previously (Figure 3).2,34 Stearic acid (50 mg) and injectable soya lecithin (30 mg) were accurately weighted and dissolved in 10 mL acetone. The organic phase was added, dropwise, into the 0.1% Dexa-LHON solution, which was being stirred at 600 rpm at room temperature. When complete evaporation of the organic solvent occurred, the redundant stabilizers were separated by ultracentrifugation at 1000 g, 4°C, for 20 min. The pellet was vortexed and resuspended in Milli-Q water, washed three times, filtered through a 0.45 μm membrane, and adjusted to pH 7.0 ± 0.1 with sodium hydroxide. The obtained SLN suspensions were stored at 2°C–8°C. Non-Dexa-SLNs were prepared in the same manner, but using LHON without Dexa.


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)

Preparation of Tf-PEG-PE-modified SLNs/pEGFP. Abbreviations: SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Tf, transferrin; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-7-2513: Preparation of Tf-PEG-PE-modified SLNs/pEGFP. Abbreviations: SLNs, solid lipid nanoparticles; pEGFP, enhanced green fluorescence protein plasmid; Tf, transferrin; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine.
Mentions: SLNs were prepared following the nanoprecipitation method (solvent displacement technique), as described previously (Figure 3).2,34 Stearic acid (50 mg) and injectable soya lecithin (30 mg) were accurately weighted and dissolved in 10 mL acetone. The organic phase was added, dropwise, into the 0.1% Dexa-LHON solution, which was being stirred at 600 rpm at room temperature. When complete evaporation of the organic solvent occurred, the redundant stabilizers were separated by ultracentrifugation at 1000 g, 4°C, for 20 min. The pellet was vortexed and resuspended in Milli-Q water, washed three times, filtered through a 0.45 μm membrane, and adjusted to pH 7.0 ± 0.1 with sodium hydroxide. The obtained SLN suspensions were stored at 2°C–8°C. Non-Dexa-SLNs were prepared in the same manner, but using LHON without Dexa.

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