A New Triantennary Galactose-Targeted PEGylated Gene Carrier, Characterization of Its Complex with DNA, and Transfection of Hepatoma Cells
文摘
Nonviral gene vectors remain inefficient in vivo largely because of their rapid clearance from thecirculation and also their nonspecific association with the extracellular matrix. To overcome suchdrawbacks, cationic lipoplexes are now frequently coated with hydrophilic polymers such as PEGs toreduce nonspecific interactions, and ligands are also linked to their surface to obtain cell-specific genetransfer. In view of the development of vectors for systemic gene delivery, we have designed andstudied lipoplexes that carry a triantennary galactosyl ligand attached to the distal end of a (PEG)45-conjugated lipid. We incorporated this targeted PEGylated lipid into lipoplexes using two strategiesof formulation, i.e., using either preformed micelles or liposomes. We demonstrated that theincorporation of PEG chains stabilized lipoplexes and masked, but only partially, the positive chargesexposed on the surface of the particles. We have also shown that incorporation into lipoplexes of alipidated PEG chain, bearing a ligand at its distal end, yielded particles that exhibited an accessibleligand throughout the whole range of cationic lipid to DNA ratios. We obtained a targeted transfectionin HepG2 cells with one of the formulations. Our results strengthen the validity of using a ligandcarried by a long PEG spacer arm for targeted gene transfer.
