Abstract
5'-phosphatidyl-FURs, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by a cytotoxic nucleosides, 5-fluorouridine(FUR), were designed to be potent antitumor agents. 5'-phosphatidyl-FURs were synthesized by transphosphatidylation catalyzed by phospholipase D from phosphatidylcholines and FUR, and showed greater antitumor activity than FUR. We demonstrated that a 5'-phosphatidyl-FUR given orally was absorbed via a specific pathway for natural phospholipids, namely deacylation-reacylation cycle, to be transported highly selectively to lymph in rats, which suggested effective use of antitumor pseudo-phospholipids, in targeting chemotherapy of metastases of tumors. In fact, 5'-phosphatidyl-FUR showed significant antitumor activity both against P388 leukemia metastasized to the lymph node and P815 mastocytoma metastasized to the lever in mice. These results suggested that the pseudo-phospholipids could be recognized as phospholipids by the body. This methodology of DDS would be applicable for various antitumor agents as well as other biologically active compounds.
