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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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Related in: MedlinePlus

General reaction scheme for synthesis of Tf-PEG-PE.Abbreviations: DMSO, dimethylsulfoxide; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine; TEA, triethylamine; Tf, transferrin.
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f2-ijn-7-2513: General reaction scheme for synthesis of Tf-PEG-PE.Abbreviations: DMSO, dimethylsulfoxide; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine; TEA, triethylamine; Tf, transferrin.

Mentions: Tf-PEG-PE ligands were synthesized as described in Figure 2. Maleimide-PEG2000-COOH (100 mg) was dissolved with dimethyl sulfoxide (DMSO) and stirred with PE (36 mg) as a mixture. 1-[3-(dimethylamino)propyl]-3- ethylcarbodiimide (EDC · HCl) (72 mg) and triethylamine (TEA, 1 equivalent of EDC · HCl) were dissolved in DMSO, added, dropwise into the mixture in an ice bath, and stirred for 36 hours, to produce Maleimide-PEG-CO-NH-PE. Tf was first modified with 1 equivalent of Traut’s reagent to complete thiolation of Tf.40 The thiolated Tf was then added to the Maleimide-PEG2000-COOH solution, and the mixture was incubated for 2 hours at room temperature, with gentle stirring. The product was dialyzed against Milli-Q water for 24 hours to form Tf-PEG-PE solution. The mixture was centrifuged at 10,000 g for 30 min at 4°C, and then resuspended in PBS (pH 7.4).


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)

General reaction scheme for synthesis of Tf-PEG-PE.Abbreviations: DMSO, dimethylsulfoxide; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine; TEA, triethylamine; Tf, transferrin.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-7-2513: General reaction scheme for synthesis of Tf-PEG-PE.Abbreviations: DMSO, dimethylsulfoxide; PEG, polyethylene glycol; PE, L-α-phosphatidylethanolamine; TEA, triethylamine; Tf, transferrin.
Mentions: Tf-PEG-PE ligands were synthesized as described in Figure 2. Maleimide-PEG2000-COOH (100 mg) was dissolved with dimethyl sulfoxide (DMSO) and stirred with PE (36 mg) as a mixture. 1-[3-(dimethylamino)propyl]-3- ethylcarbodiimide (EDC · HCl) (72 mg) and triethylamine (TEA, 1 equivalent of EDC · HCl) were dissolved in DMSO, added, dropwise into the mixture in an ice bath, and stirred for 36 hours, to produce Maleimide-PEG-CO-NH-PE. Tf was first modified with 1 equivalent of Traut’s reagent to complete thiolation of Tf.40 The thiolated Tf was then added to the Maleimide-PEG2000-COOH solution, and the mixture was incubated for 2 hours at room temperature, with gentle stirring. The product was dialyzed against Milli-Q water for 24 hours to form Tf-PEG-PE solution. The mixture was centrifuged at 10,000 g for 30 min at 4°C, and then resuspended in PBS (pH 7.4).

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