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

被引:38
作者
Tiukinhoy, SD
Mahowald, ME
Shively, VP
Nagaraj, A
Kane, BJ
Klegerman, ME
MacDonald, RC
McPherson, DD
Matsumura, JS
机构
[1] Northwestern Univ, Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA
[2] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL USA
关键词
liposomes; cationic lipid; echogenic; transfection; gene therapy;
D O I
10.1097/00004424-200012000-00007
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
RATIONALE AND OBJECTIVES. Echogenic antibody-conjugated anionic liposomes have been developed that allow directed tissue targeting and acoustic enhancement. These are not efficient for gene delivery. A cationic formulation that allows directed gene delivery while retaining acoustic properties may provide more efficient transfection. METHODS. Cationic Liposomes were prepared and acoustic reflectivity was determined. Anti-fibrinogen-conjugated liposomes were laid on fibrin-coated slides and adherence was quantified using fluorescence techniques. Liposomes were combined with a reporter gene and plated on cell cultures. Human umbilical vein endothelial cells were stimulated to upregulate intercellular adhesion molecule-1 (ICAM-1) and were treated with anti-ICAM-1-conjugated liposomes, and gene expression was quantified. RESULTS. Cationic liposomes retained their acoustic reflectivity and demonstrated specific adherence to fibrin under how conditions. Significant transfection of human umbilical vein endothelial cells was demonstrated, with higher 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 modification. This presents exciting potential for a vector that allows tissue enhancement and targeted gene delivery.
引用
收藏
页码:732 / 738
页数:7
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