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 activ ity. F-MTX conjugates were synthesized in reaction of fibrinogen with MTX N -hydroxysuccynimide ester. The conjugates were not cross-linked and were so luble 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-M TX conjugate in mice with P388 leukemia as compared with MTX alone; (3) a s ignificantly increased in vivo lethal toxicity of F-MTX as compared with MT X. The results suggest the therapeutic utility of the fibrinogen-methotrexa te conjugate and the usefulness of fibrinogen as a chemotherapeutic drug ca rrier. However, a new effort in the preparation of F-MTX conjugate should b e made to decrease its in vivo toxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.