Energy-Independent Intracellular Gene Delivery Mediated by Polymeric Biomimetics of Cell-Penetrating Peptides

Efficient gene transfer into mammalian cells mediated by small molecular amphiphile-polymer conjugates, bile acid-polyethylenimine (BA-PEI), is demonstrated, opening an efficient transport route for genetic materials across the cell membrane. This process occurs without the aid of endocytosis or other energy-consuming processes, thus mimicking macromolecular transduction by cell-penetrating peptides. The exposure of a hydrophilic face of the amphiphilic BA moiety on the surface of BA-PEI/DNA complex that mediates direct contact of the BA molecules to the cell surface seems to play an important role in the endocytosis- and energy-independent internalization process. The new modality of the polymeric biomimetics can be applied to enhanced delivery of macromolecular therapeutics. Small-molecular amphiphile/polymer conjugates mediate internalization of plasmid DNA to mammalian cells without the aid of endocytosis or other energy-consuming processes, which mimics macromolecular transduction phenomenon by cell penetrating peptides. This novel modality of polymeric biomimetics can be applied to where cell penetrating peptides is required for enhanced delivery of macromolecules.