Abstract
Polyethylenimine (PEI) is one of the most potent synthetic gene delivery vectors because of its high transfection efficiency. Although PEI has been used as a delivery vehicle for a long while, its toxicity is always an issue for clinical applications. In this study, we introduced a low molecular weight PEI of 10 kilodaltons to chondroitin sulfate (CS) via a Michael addition method. By adjusting weight ratios between cationic PEI and anionic CS, the intermolecular or intramolecular, or both, electrostatic interactions of CS-modified PEI (CP) maintained good water solubility but lost some ability to permeate cell membranes. Thus, the cytotoxicity of PEI decreased without sacrificing its gene transfection efficiency. Three CP copolymers with different PEI contents were synthesized and used to prepare polyplexes with plasmid DNA. The pDNA-formed polyplex with a low PEI content (CP(L)) was least cytotoxic and had a transfection efficiency comparable to Lipofectamine/pDNA. The good uptake of CP(L)/pDNA into U87 cells was primarily based on clatherin-dependent and CD44-mediated endocytosis.
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