n-(1-(2-3-dioleyloxy)propyl)-n-n-n-trimethylammonium-chloride and Peritoneal-Neoplasms

Peritoneal dissemination remains the most difficult type of metastasis to treat, and current systemic chemotherapy or radiotherapy tends to have little effect; therefore, immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach. Recently, we have reported that intraperitoneal administration of phosphodiester (PO) CpG DNA-lipoplex could efficiently inhibit peritoneal dissemination in mice. In this study, chemically modified phosphorothioate (PS)-CpG DNA and natural PO-CpG DNA were complexed with DOTMA/cholesterol cationic liposomes (PS-CpG DNA-lipoplex and PO-CpG DNA-lipoplex) and their antitumor activity was evaluated in a mouse model of peritoneal dissemination. Intraperitoneal administration of the PS-CpG DNA-lipoplex inhibited the proliferation of tumor cells in the greater omentum and the mesentery more efficiently than PO-CpG DNA-lipoplex. PS-CpG DNA-lipoplex induced higher cytokine production from primary cultured mouse peritoneal macrophages, suggesting that the high antitumor activity of the PS-CpG DNA-lipoplex is mediated by a high rate of cytokine production from immunocompetent cells such as macrophages. The serum transaminase levels of mice receiving intraperitoneal PS-CpG DNA-lipoplex treatment were measured to evaluate systemic toxicity, and these were found to be the same as those of untreated mice. These results suggest that intraperitoneal administration of PS-CpG DNA-lipoplex could be efficient immunotherapy for peritoneal dissemination.

Topics: Animals; Cations; Cell Line, Tumor; Cholesterol; Cytokines; DNA; Female; Immunotherapy; Liposomes; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Oligodeoxyribonucleotides; Particle Size; Peritoneal Neoplasms; Phosphorothioate Oligonucleotides; Quaternary Ammonium Compounds; Xenograft Model Antitumor Assays