Fluorinated intermediate molecular weight polyethylenimine (FP2ks) with various fluorination degrees was synthesized by conjugation with heptafluorobutyric anhydride and the fluorination effect for gene delivery systems was examined. FP2ks could condense pDNA, forming compact, positively charged, and nano-sized spherical particles. It was thought that their decreased electrostatic interaction with pDNA would be compensated by hydrophobic interaction. The cytotoxicity of FP2ks was increased with the increase of fluorination degree, probably due to the cellular membrane disruption via hydrophobic interaction with FP2ks. The transfection efficiency of highly fluorinated FP2ks was not severely affected in serum condition, assuming their good serum-compatibility. Discrepancy between their higher cellular uptake efficiency and lower transfection efficiency than PEI25k was thought to arise from the formation of compact polyplexes followed by the decreased dissociation of pDNA. It was also suggested that multiple energy-dependent cellular uptake mechanisms and endosome buffering would mediate the transfection of FP2ks.
Keywords: fluorination; gene delivery systems; polyethylenimine 1.8k; serum-compatibility; transfection mechanism.
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