Enhancement of tumouricidal activity of daunomycin by receptor-mediated delivery. In vivo studies.

A conjugate of the antineoplastic drug daunomycin (DNM) with maleylated bovine serum albumin (MBSA) bound to the transformed cells of a macrophage lineage with high affinity and saturation kinetics through scavenger receptors present on the surface of macrophages. Binding of MBSA-DNM by these cells led to efficient internalization and degradation of the ligand. When injected into mice, the drug conjugate was cleared rapidly from the circulation and accumulated in the macrophage-rich tissues, viz. liver, lung and spleen. MBSA-DNM suppressed the growth of J774A.1 tumour cells in BALB/C mice at much lower dosages of DNM relative to the free form of the drug. Thus, 50% reduction of the tumour mass was elicited by 0.8 micrograms of DNM in the conjugated form, whereas approximately 28 micrograms of the drug in the free form was necessary to achieve a similar antitumour effect. These findings merit serious consideration in the development of new chemotherapeutic agents for the treatment of histiocytic malignancies that involve cells of macrophage lineage bearing the scavenger receptors.