LIPOSOME-MEDIATED DELIVERY OF GALLIUM TO MACROPHAGE-LIKE CELLS IN-VITRO - DEMONSTRATION OF A TRANSFERRIN-INDEPENDENT ROUTE FOR INTRACELLULAR DELIVERY OF METAL-IONS

Gallium (Ga) prevents the activation of macrophages and might be usefu l as an immunosuppressive agent. It is taken up by the malignant cells through the transferrin (Tf) receptor pathway, but this pathway may b e insufficient in the case of non-malignant cells. We studied the Tf-i ndependent, liposome-mediated delivery of Ga to macrophage-like cells in vitro by a growth inhibition assay. The growth inhibitory propertie s of Ga for other types of cells was also evaluated. Ga complexed with nitrilotriacetate (GaNTA) and encapsulated in DSPG-liposomes was 16 a nd 48 times more potent for RAW 264 cells than free GaNTA and Ga-nitra te, respectively. CV I-P cells were also somewhat sensitive to liposom al Ga, but other cell lines with lower endocytotic capacity were insen sitive. The inhibition of RAW 264 cell growth induced by liposomal or free GaNTA was partially reversed with iron-loading of the cells, indi cating that this form of Ga causes an intracellular iron deficiency si milar to that produced by Tf-bound Ga. Our results indicate that encap sulation of Ga in negatively charged liposomes provides a transferrin independent route for intracellular delivery of the compound to macrop hages, which is of special interest in the treatment of autoimmune dis eases, such as rheumatoid arthritis.