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Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Synthetic oligodeoxynucleotides containing CpG motifs (CpG DNA) can activate immunocompetent cells, which may possess antitumor activity. Previously, we found that when the cationic liposomes complexes formed with CpG DNA (CpG DNA lipoplex) were administered intranasally, they could prevent pulmonary metastasis in mice. However, the mechanisms underlying this process are unknown. In the present study, we show that natural killer (NK) cells play an important role in preventing pulmonary metastasis and peritoneal dissemination in a mouse model of metastatic disease. Further, in vitro, the NK cells obtained from mice treated with CpG DNA lipoplex showed higher cytotoxicity compared with untreated mice and in vivo, depletion of NK cells (achieved through injection of rabbit anti-asialo GM1 serum), abolished the inhibitory effect of CpG DNA lipoplex on pulmonary metastasis and peritoneal dissemination. In contrast, macrophage elimination did not disrupt the effects of the CpG DNA lipoplex. These results suggest that intranasal administration of CpG DNA lipoplex could prevent pulmonary metastasis and peritoneal dissemination by activating NK cells.
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