title: High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells.
abstract: OBJECTIVE
  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 microg/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 microg/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 microg/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 microg/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, School of Pharmacy, Fudan University, Shanghai 200032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lou
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Liao
authors.forename: Man-Ping
authors.initials: MP
authors.lastname: Wu
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Cheng
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Yin
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fei
mesh_terms: D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008075:Lipoproteins, HDL / Q000493:pharmacokinetics*; D008113:Liver Neoplasms
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008075:Lipoproteins, HDL; C011157:aclacinomycins; D015250:Aclarubicin
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