We reported previously that sulfoquinovosyl
diacylglycerol and sulfoquinovosyl
monoacylglycerol (SQDG/SQMG) are potent inhibitors of mammalian
DNA polymerases and
DNA topoisomerase II, and can be potent
immunosuppressive agents and anticancer
chemotherapy agents [Matsumoto, Y., Sahara, H., Fujita T., Shimozawa, K., Takenouchi, M., Torigoe, T., Hanashima, S., Yamazaki, T., Takahashi, S., Sugawara, F., et al., An Immunosuppressive Effect by Synthetic
Sulfonolipids Deduced from Sulfonoquinovosyl
Diacylglycerols of Sea Urchin,
Transplantation 74, 261-267 (2002); Sahara, H., Hanashima, S., Yamazaki, T., Takahashi, S., Sugawara, F., Ohtani, S., Ishikawa, M., Mizushina, Y., Ohta, K., Shimozawa, K., et al., Anti-
tumor Effect of Chemically Synthesized
Sulfolipids Based on Sea Urchin's Natural Sulfonoquinovosylmonoacylglycerols, Jpn. J.
Cancer Res. 93, 85-92 (2002)]. In those experiments, the in vivo effectiveness greatly depended on the degree of water solubility of SQDG/SQMG. In the present work, we studied the emulsification of SQDG/SQMG in terms of their use in in vivo experiments.
Lipid emulsions containing SQDG/SQMG (oil-in-water
emulsions) in which the particle size was smaller than 100 nm were designed and synthesized, and then the biochemical modes of emulsified SQDG/SQMG were studied in comparison with those of SQDG/SQMG solubilized by
DMSO. Emulsified SQDG/SQMG are also selective mammalian
DNA polymerase inhibitors and potent
antineoplastic agents but do not inhibit the
DNA topoisomerase II activity. The growth inhibition effect of emulsified SQMG to NUGC-3
cancer cells was twofold stronger than
DMSO-soluble SQMG (69 and 151 microM, respectively). From these results, the properties of
lipid emulsions containing SQDG/SQMG and their possible use in in vivo experiments including clinical use are discussed.