Abstract
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC), a novel antitumor nucleoside antimetabolite, has a new mechanism of action for damaging tumor cells. This compound showed potent growth inhibitory activity against various kinds of human tumor cells both in vitro and in vivo. Furthermore, 5'-phosphatidylation of the compound enhanced the antitumor activity. In the present study, we liposomalized 5'-O-dipalmitoylphosphatidyl derivative of CNDAC (DPP-CNDAC) and investigated the effect of DPP-CNDAC incorporation on the in vivo behavior of these liposomes by a non-invasive method using positron emission tomography (PET). Interestingly, liposomes composed of DPP-CNDAC and cholesterol (DPP-CNDAC/CH liposomes) were observed to have a tendency to accumulate in lungs. Furthermore, this accumulation was markedly enhanced in the mice bearing lung metastatic cancer. Therefore, we attempted to use these CNDAC/CH liposomes for lung targeting and to examine the therapeutic efficacy against lung metastatic cancer. In experimental model using highly lung metastatic murine B16BL6 melanoma cells, these liposomes significantly reduced the number of lung tumor colonies as well as the size of them in a dose dependent manner. On the contrary, reduced lung colonization was not seen by use of the formulation of conventional liposomes or soluble CNDAC. These results were coincident with the data of PET analysis, and suggesting the usefulness of DPP-CNDAC/CH liposomes for curing lung metastasis.
