Mannosylated Cationic Liposomes/CpG DNA Complex for the Treatment of Hepatic Metastasis after Intravenous Administration in Mice

Immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach to combat refractory hepatic metastasis. In this study, we report the use of a conventional cationic liposomes/CpG DNA complex (Bare/CpG DNA lipoplex) and a mannosylated cationic liposomes/CpG DNA complex (Man/CpG DNA lipoplex) for effective inhibition of hepatic metastasis in mice. After intravenous administration of Bare/CpG DNA lipoplex, higher amounts of IL-12 and IFN-γ were produced in serum or liver compared with naked CpG DNA, and their production was increased further by Man/CpG DNA lipoplex. Then, Bare/CpG DNA lipoplex and Man/CpG DNA lipoplex were administered intravenously to hepatic metastasis model mice, and the numbers of tumor cells (colon26/Luc) were quantitatively assayed. The number of tumor cells in Man/CpG DNA lipoplex-treated mice was same as those in Bare/CpG DNA lipoplex-treated mice. These results suggest that intravenous administration of not only Bare/CpG DNA lipoplex but also Man/CpG DNA lipoplex could be an efficient immunotherapy for hepatic metastasis. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1193-1197, 2009