title: Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells.
abstract: Kupffer cells in livers bearing tumor metastases were found to have promoted tumor invasion and exacerbated the metastasis. This implies that the function of Kupffer cells might differ between animals bearing hepatic metastases and those that are healthy. Kupffer cells are considered responsible for the accumulation of liposomes in the liver. In this study, we hypothesized that the alteration in the function of Kupffer cells by hepatic metastasis would also affect the biodistribution of liposomes following intravenous administration. The hepatic accumulation and the blood concentration of PEGylated liposomes were compared between healthy mice and tumor-bearing mice. We noted that hepatic accumulation and elimination from the blood were significantly accelerated in tumor-bearing mice, indicating that our hypothesis was correct. In the tumor-bearing mice, the proportion of Kupffer cells taking up liposomes was significantly increased. Intravenous injection of oxaliplatin (l-OHP) containing PEGylated liposomes decreased the fraction of Kupffer cells, but this administration caused no injury to the hepatocytes. These results suggest that PEGylated liposomes containing l-OHP may have the potential to treat metastatic hepatic cancer-not only via the direct killing of the cancer cells but also via a reduction in tumor-supportive Kupffer cells.
authors.affiliation: Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Biomedical Sciences, Tokushima University.
authors.forename: Masami
authors.initials: M
authors.lastname: Ukawa
authors.forename: Yukako
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ando
authors.forename: Taro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007728:Kupffer Cells / Q000378:metabolism*; D008081:Liposomes; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000378:metabolism; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D012509:Sarcoma / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011092:Polyethylene Glycols