Liver Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2005; 11(7): 954-959
Published online Feb 21, 2005. doi: 10.3748/wjg.v11.i7.954
High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells
Bin Lou, Xue-Ling Liao, Man-Ping Wu, Pei-Fang Cheng, Chun-Yan Yin, Zheng Fei
Bin Lou, Xue-Ling Liao, Man-Ping Wu, Pei-Fang Cheng, Chun-Yan Yin, Zheng Fei, Department of Biochemistry, School of Pharmacy, Fudan University, Shanghai 200032, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Man-Ping Wu, Department of Biochemistry, School of Pharmacy, Fudan University, Shanghai 200032, China. mpwu@shmu.edu.cn
Telephone: +86-21-64042268 Fax: +86-21-64042268
Received: June 8, 2004
Revised: June 10, 2004
Accepted: July 11, 2004
Published online: February 21, 2005
Abstract

AIM: To investigate the possibility of recombinant high-density lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.

METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.

RESULTS: The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 µg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 µg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs 3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells.

CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes. HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.

Keywords: High-density lipoprotein, Carrier, Antitumoral drug, SMMC-7721 hepatoma cell