Enhanced intracellular delivery of doxorubicin by scavenger receptor-mediated endocytosis for preferential killing of histiocytic lymphoma cells in culture.
A conjugate of the antineoplastic drug doxorubicin (DXR) with maleylated bovine serum albumin (MBSA) was taken up by a human histiocytic lymphoma cell line (U937) through the high efficiency process of scavenger receptor-mediated endocytosis resulting in a sixfold higher intracellular concentration of the drug compared to that obtained when the free drug was administered. Compared to the free drug, the drug conjugate showed significantly higher cytotoxicity towards U937 cells presumably because of intracellular availability of a pharmacologically active form of the drug. The intracellular product released after lysosomal degradation of the drug conjugate was chromatographically identical to free DXR. These findings merit serious consideration in the development of new chemotherapeutic agents for the treatment of histiocytic malignancies.
Basu
S
S
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Mukhopadhyay
B
B
Basu
S K
SK
Mukhopadhyay
A
A
D000418:Albumins / Q000737:chemistry; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004317:Doxorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D066298:In Vitro Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008565:Membrane Proteins; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine
D000418:Albumins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C049877:maleylalbumin; D012710:Serum Albumin, Bovine; D004317:Doxorubicin; D004247:DNA