An Approach to Transgene Expression in Liver Endothelial Cells Using a Liposome-Based Gene Vector Coated with Hyaluronic Acid

作者：Yamada Yuma; Hashida Masahiro; Hayashi Yasuhiro; Tabata Mai; Hyodo Mamoru; Ara Mst Naznin; Ohga Noritaka; Hida Kyoko; Harashima Hideyoshi^*

来源：Journal of Pharmaceutical Sciences, 2013, 102(9): 3119-3127.

DOI：10.1002/jps.23480

• hyaluronic acid
• liver endothelial cell
• multifunctional envelope-type nano device
• transgene expression
• non-viral gene vector
• DNA delivery
• liposomes
• nanotechnology
• plasmid DNA
• transfection

Dysfunctional sinusoidal liver endothelial cells (LECs) are associated with liver diseases, such as liver fibrosis, cirrhosis, and portal hypertension. Because of this, gene therapy targeted to LECs would be a useful and productive strategy for directly treating these diseases at the level of genes. Here, we report on the development of a transgene vector that specifically targets LECs. The vector is a liposome-based gene vector coated with hyaluronic acid (HA). HA is a natural ligand for LECs and confers desirable properties on particles, rendering them biodegradable, biocompatible, and nonimmunogenic. In this study, we constructed HA-modified carriers, and evaluated cellular uptake and transfection activity using cultured LECs from KSN nude mice (KSN-LECs). Cellular uptake analyses showed that KSN-LECs recognized the HA-modified carriers more effectively than skin endothelial cells. The transfection assay indicated that the efficient gene expression in KSN-LECs, using the HA-modified carriers, required an adequate lipid composition and a functional device to control intracellular trafficking. This finding contributes to our overall knowledge of transgene expression targeted to LECs.

• 出版日期2013-9