Different strategies for formation of pegylated EGF-conjugated PEI/DNA complexes for targeted gene delivery
| Autor: | Ralf Kircheis, Ernst Wagner, Thomas Blessing, Robert Holzhauser, Malgorzata Kursa |
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| Rok vydání: | 2001 |
| Předmět: |
Macromolecular Substances
Biomedical Engineering Pharmaceutical Science Gene Expression Bioengineering Gene delivery Transfection KB Cells Polyethylene Glycols chemistry.chemical_compound Mice Epidermal growth factor PEG ratio Tumor Cells Cultured Animals Humans Polyethyleneimine Luciferases Pharmacology Polyethylenimine Epidermal Growth Factor Chemistry Rectal Neoplasms Organic Chemistry technology industry and agriculture Gene Transfer Techniques DNA Molecular biology Endocytosis Kidney Neoplasms ErbB Receptors Epidermoid carcinoma hormones hormone substitutes and hormone antagonists Biotechnology Conjugate |
| Zdroj: | Bioconjugate chemistry. 12(4) |
| ISSN: | 1043-1802 |
| Popis: | With the aim of generating gene delivery systems for tumor targeting, we have synthesized a conjugate consisting of polyethylenimine (PEI) covalently modified with epidermal growth factor (EGF) peptides. Transfection efficiency of the conjugate was evaluated and compared to native PEI in three tumor cell lines: KB epidermoid carcinoma cells, CMT-93 rectum carcinoma cells, and Renca-EGFR renal carcinoma cells. Depending on the tumor cell line, incorporation of EGF resulted in an up to 300-fold increased transfection efficiency. This ligand-mediated enhancement and competition with free EGF strongly suggested uptake of the complexes through the EGF receptor-mediated endocytosis pathway. Shielded particles being crucial for systemic gene delivery, we studied the effect of covalent surface modification of EGF-PEI/DNA complexes with a poly(ethylene glycol) (PEG) derivative. An alternative way for the formation of PEGylated EGF-containing complexes was also evaluated where EGF was projected away from PEI/DNA core complexes through a PEG linker. Both strategies led to shielded particles still able to efficiently transfect tumor cells in a receptor-dependent fashion. These PEGylated EGF-containing complexes were 10- to 100-fold more efficient than PEGylated complexes without EGF. |
| Databáze: | OpenAIRE |
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