Tumor targeting with surface-shielded ligand-polycation DNA complexes

Incorporation of the receptor binding ligands transferrin (Tf) or epidermal growth factor (EGF) into DNA/polyethylenimine (PEI) complexes was found to enhance gene transfer into tumor cell lines in a receptor-dependent manner . In systemic applications, the surface charge of DNA complexes dominated t he in vivo characteristics of gene transfer. Administration of surface-shie lded Tf-polycation/DNA complexes into the tail vein of A/J mice resulted in preferential gene delivery into distantly growing subcutaneous Neuro2a tum ors. In contrast, application of positively charged DNA/PEI complexes direc ted gene transfer primarily to the lung. Two alternatives of masking the su rface charge of complexes were accomplished. In the first ease, shielding w as obtained by covalently coating of DNA/Tf-PEI complexes with polyethylene glycol (PEG). Alternatively, incorporation of sufficient Tf protein into t he DNA complexes resulted in charge shielding even without PEGylation. In t he latter case lower-molecular weight polycations (25 kDa PEI for Tf-PEI co mplexes, or 32 kDa polylysine for AVET complexes) were used. (C) 2001 Elsev ier Science B.V. All rights reserved.