Use of mannosylated cationic liposomes/ immunostimulatory CpG DNA complex for effective inhibition of peritoneal dissemination in mice

✍ Scribed by Yukari Kuramoto; Shigeru Kawakami; Shuwen Zhou; Kyouichi Fukuda; Fumiyoshi Yamashita; Mitsuru Hashida

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 181 KB
• Volume: 10
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1162

✦ Synopsis

Abstract

Background

Immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach to combat refractory peritoneal dissemination. In the present study, we report the use of a mannosylated cationic liposomes/immunostimulatory CpG DNA complex (Man/CpG DNA lipoplex) for effective inhibition of peritoneal dissemination in mice.

Methods

The immune response characteristics of the Man/CpG DNA lipoplex were evaluated by measuring tumor necrosis factor (TNF)‐α production using primary cultured mouse peritoneal macrophages. Subsequently, Man/CpG DNA lipoplex was administered intraperitoneally (i.p.) to peritoneal dissemination model mice, and the number of tumor cells (colon26/Luc) was quantitatively evaluated by measuring luciferase activity. The effect on survival time of the Man/CpG DNA lipoplex was also investigated. The serum transaminase levels of mice receiving i.p. Man/CpG DNA lipoplex treatment were measured to evaluate systemic toxicity.

Results

The Man/CpG DNA lipoplex induced higher TNF‐α production from macrophages than CpG DNA complexed with conventional cationic liposomes and galactosylated cationic liposomes (Bare/CpG DNA lipoplex and Gal/CpG DNA lipoplex), suggesting mannose receptor‐mediated CpG DNA transfer. Intraperitoneal administration of Man/CpG DNA lipoplex inhibited the proliferation of tumor cells in the greater omentum and the mesentery more efficiently than Bare/CpG DNA lipoplex and Gal/CpG DNA lipoplex. Furthermore, the survival time of the peritoneal dissemination model mice was prolonged by i.p. administration of Man/CpG DNA lipoplex. The serum transaminase levels of mice receiving i.p. Man/CpG DNA lipoplex were found to be the same as those of untreated mice.

Conclusions

The results obtained suggest that i.p. administered Man/CpG DNA lipoplex can be used for efficient immunotherapy to combat peritoneal dissemination. Copyright © 2008 John Wiley & Sons, Ltd.