Synthesis of Polyethylenimine-Based Nanocarriers for Systemic Tumor Targeting of Nucleic Acids

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Abstract

Nucleic acid-based therapies offer the option to treat tumors in a highly selective way, while toxicity towards healthy tissue can be avoided when proper delivery vehicles are used. We have recently developed carrier systems based on linear polyethylenimine, which after chemical coupling of proteinous or peptidic ligands can form nanosized polyplexes with plasmid DNA or RNA and deliver their payload into target cells by receptor-mediated endocytosis. This chapter describes the synthesis of linear PEI (LPEI) from a precursor polymer and the current coupling techniques and purification procedure for peptide conjugates with linear polyethylenimine. A protocol is also given for the formation and characterization of polyplexes formed with LPEI conjugate and plasmid DNA.