title: Galactosylated poly(ethyleneglycol)-lithocholic Acid selectively kills hepatoma cells, while sparing normal liver cells.
abstract: Delivering drugs selectively to cancer cells but not to nearby normal cells is a major obstacle in drug therapy. In this study, lithocholic acid (LCA), a potent anti-cancer drug, is converted to two forms of poly(ethyleneglycol) (PEG) conjugates, viz., PEG-LCA (PL) and lactobionic acid (LBA) conjugated PEG-LCA (LPL). The latter form contains a galactose ligand in LBA to target the hepatocytes. Both forms are self-assembled to form nanoparticle formulation, and they have high potency than LCA to kill HepG2 cancer cells, sparing normal LO2 cells. Besides, LPL has high specificity to mouse liver cells in vivo. Western blot results confirm that the cell death is occurred through apoptosis induced by LPL nanoparticles. In conclusion, the induction of apoptosis and cell death is much more efficient with LPL nanoparticles than LCA molecules.
authors: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
authors: Nomundelger
authors: N
authors: Gankhuyag
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea.
authors: Bijay
authors: B
authors: Singh
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea.
authors: Sushila
authors: S
authors: Maharjan
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea.
authors: Yun-Jaie
authors: YJ
authors: Choi
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea. chocs@snu.ac.kr.
authors: Chong-Su
authors: CS
authors: Cho
authors: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea. mchotox@snu.ac.kr.
authors: Myung-Haing
authors: MH
authors: Cho
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008095:Lithocholic Acid / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D011092:Polyethylene Glycols; D008095:Lithocholic Acid; C000595209:polyethylene glycol 1000
keywords: anti-cancer drugs; apoptosis; hepatocyte-specific; lithocholic acid; nanoparticles