Optimization of Liganded Polyethylenimine Polyethylene Glycol Vector for Nucleic Acid Delivery
| Autor: | Maya Zigler, Anna Sagalov, Nufar Edinger, Alexei Shir, Neta Pessah, Yair Razvag, Shoshana Klein, Alexander Levitzki, Meital Reches, Salim Joubran |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Receptor
ErbB-2 Recombinant Fusion Proteins Biomedical Engineering Pharmaceutical Science Bioengineering Polyethylene glycol Conjugated system Ligands Transfection Polyethylene Glycols chemistry.chemical_compound Epidermal growth factor Cell Line Tumor PEG ratio Humans Polyethyleneimine Moiety Sulfhydryl Compounds Pharmacology Drug Carriers Polyethylenimine Deoxyribonucleases Organic Chemistry technology industry and agriculture DNA Combinatorial chemistry Protein Structure Tertiary 3. Good health Molecular Weight chemistry Biochemistry Nucleic acid Biotechnology Conjugate |
| Zdroj: | Bioconjugate Chemistry |
| ISSN: | 1043-1802 |
| DOI: | 10.1021/bc500252a |
| Popis: | The delivery of nucleic acids into cells is an attractive approach for cancer therapy. Polyethylenimine (PEI) is among the most efficient nonviral carriers. Recent studies have demonstrated that PEI can be conjugated to targeting ligands, such as epidermal growth factor (EGF) and transferrin (Schaffert et al., 2011; Abourbeh et al., 2012; Ogris et al., 1999). Herein we present a simplified protocol for producing homogeneous preparations of PEGylated linear PEI: LPEI-PEG2k. We generated two well-characterized copolymers, with ratios of LPEI to PEG of 1:1 and 1:3. These copolymers were further conjugated through disulfide bonds to a Her-2 targeting moiety, Her-2 affibody. This reaction yielded two triconjugates that target Her-2 overexpressing tumors. Polyplexes were formed by complexing plasmid DNA with the triconjugates. We characterized the biophysical properties of the conjugates, and found that the triconjugate 1:3 polyplex had lower ζ potential, larger particle size, and more heterogeneous shape than the triconjugate 1:1 polyplex. Triconjugate 1:1 and triconjugate 1:3 polyplexes were highly selective toward cells that overexpress Her-2 receptors, but triconjugate 1:1 polyplex was more efficient at gene delivery. Our studies show that the biophysical and biological properties of the conjugates can be profoundly affected by the ratio of LPEI:PEG2k:ligand. The procedure described here can be adapted to generate a variety of triconjugates, simply by changing the targeting moiety. |
| Databáze: | OpenAIRE |
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