Development of echogenic, plasmid-incorporated, tissue-targeted cationic liposomes that can be used for directed gene delivery

RATIONALE AND OBJECTIVES. Echogenic antibody-conjugated anionic liposomes h ave been developed that allow directed tissue targeting and acoustic enhanc ement. These are not efficient for gene delivery. A cationic formulation th at allows directed gene delivery while retaining acoustic properties may pr ovide more efficient transfection. METHODS. Cationic Liposomes were prepared and acoustic reflectivity was det ermined. Anti-fibrinogen-conjugated liposomes were laid on fibrin-coated sl ides and adherence was quantified using fluorescence techniques. Liposomes were combined with a reporter gene and plated on cell cultures. Human umbil ical vein endothelial cells were stimulated to upregulate intercellular adh esion molecule-1 (ICAM-1) and were treated with anti-ICAM-1-conjugated lipo somes, and gene expression was quantified. RESULTS. Cationic liposomes retained their acoustic reflectivity and demons trated specific adherence to fibrin under how conditions. Significant trans fection of human umbilical vein endothelial cells was demonstrated, with hi gher gene expression seen with specific antibody-conjugated liposomes. CONCLUSIONS. Novel acoustic cationic liposomes have been developed that can be antibody conjugated for site-specific adherence and directed cell modif ication. This presents exciting potential for a vector that allows tissue e nhancement and targeted gene delivery.