Cytotoxic and antitumor effect of fibrinogen-methotrexate conjugate

In this paper we describe the chemical procedure of fibrinogen–methotrexate (F–MTX) conjugate preparation and its in vitro and in vivo antitumor activity. F–MTX conjugates were synthesized in reaction of fibrinogen with MTX N-hydroxysuccynimide ester. The conjugates were not cross-linked and were soluble in water. The results of the in vitro and in vivo studies have shown: (1) a lower in vitro cytotoxicity of the F–MTX conjugate as compared with MTX alone; (2) a significantly higher in vivo antitumor activity of the F–MTX conjugate in mice with P388 leukemia as compared with MTX alone; (3) a significantly increased in vivo lethal toxicity of F–MTX as compared with MTX. The results suggest the therapeutic utility of the fibrinogen–methotrexate conjugate and the usefulness of fibrinogen as a chemotherapeutic drug carrier. However, a new effort in the preparation of F–MTX conjugate should be made to decrease its in vivo toxicity.