Antiproliferative effect of immunoliposomes containing 5-fluorodeoxyuridine-dipalmitate on colon cancer cells

We have investigated the antiproliferative action towards CC531 colon adeno carcinoma cells of target cell-specific immunoliposomes containing the amph iphilic dipalmitoyl derivative of 5-fluorodeoxyuridine (FUdR-dP). FUdR-dP i ncorporated in immunoliposomes caused a 13-fold stronger inhibition of CC53 1 cell growth in vitro, during a 72-h treatment, than FUdR-dP in liposomes without antibody, demonstrating that the prodrug is efficiently hydrolysed to yield the active drug, FUdR, intracellularly. The intracellular release of active FUdR was confirmed by determining the fate of H-3-labelled immuno liposomal FUdR-dP. Treatments shorter than 72 h with FUdR-dP in immunolipos omes resulted in anti-tumour activities comparable to, or even higher than, that of free FUdR. The shorter treatments reflect more closely the in vivo situation and illustrate the potential advantage of the use of immunolipos omes over non-targeted liposomal FUdR-dP or free FUdR. Association of tumou r cell-specific immunoliposomes with CC531 cells was up to tenfold higher t han that of liposomes without antibody or with irrelevant IgG coupled, demo nstrating a specific interaction between liposomes and target cells which c auses an efficient intracellular delivery of the drug. Since biochemical ev idence indicates a lack of internalization or degradation of the liposomes as such; we postulate that entry of the drug most likely involves the direc t transfer of the prodrug from the immunoliposome to the cell membrane duri ng its antigen-specific interaction with the cells. followed by hydrolysis of FUdR-dP leading to relatively high intracellular FUdR-levels. In conclus ion, we describe a targeted liposomal formulation for the anticancer drug F UdR, which is able to deliver the active drug to colon carcinoma cells with high efficiency, without the need for the cells to internalize the liposom es as such.