FGF-1 as a possible carrier for targeted drug delivery

Delivery of anticancer chemotherapeuticals to tumor cells raises many problems due to pronounced systemic side effects. Targeted delivery using specific monoclonal antibodies has been postulated; however, monoclonal antibodies very often produce immune response in the human body. Chimeric and humanized antibodies have some advantages over monoclonals, but still some side effects can be observed. Because some tumor cells (e.g., breast cancer cells) overexpress fibroblast growth factor receptors, it is possible to use these receptors for drug targeting. We think that growth factors of human origin can be used for drug delivery to tumor cells. Fibroblast growth factor-1 (FGF-1) is especially suitable as drug carrier because it can cross the barrier of the cell membrane and reach the cytosol and, further, it is translocated to the cell nucleus. One possible approach for anticancer therapy is to use biotinylated growth factors linked to avidin/ streptavidin-coated liposomes. Another possibility is to link drug molecules or radioisotopes directly to growth factors. Thus, we wanted to determine if FGF-1 retains its biological activity after chemical modification, and if it is able to bind its receptors and if it can be internalized by the cells. For this purpose we have biotinylated recombinant human FGF-1 and we have verified that it retains its biological activities in NIH/3T3 and MDA-MB-453 cells and it is able to enter the target cells.