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-gamma 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.
Kuramoto
Yukari
Y
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Zhou
Shuwen
S
Fukuda
Kyouichi
K
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D002452:Cell Count; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology
C408982:CPG-oligonucleotide; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA; D008358:Mannose