Circumvention of multidrug resistance in neoplastic cells through scavenger receptor mediated drug delivery.
A conjugate of the antineoplastic drug daunomycin (DNM) with maleylated bovine serum albumin (MBSA-DNM) was taken up with high efficiency by a multidrug resistant variant, JD100, of the murine-macrophage tumour cell line, J774A.1, through the scavenger receptors resulting in cessation of DNA synthesis. In contrast, free DNM at similar concentrations did not affect the incorporation of [3H]thymidine by these cells. These results suggest that receptor-mediated intracellular delivery of antineoplastic drugs could be a viable and new approach for overcoming the problem of multidrug resistance in chemotherapy of neoplastic diseases.
Mukhopadhyay
A
A
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Mukhopadhyay
B
B
Basu
S K
SK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D004705:Endocytosis; D008264:Macrophages / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D011068:Poly G / Q000494:pharmacology; D011955:Receptors, Drug / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D008298:Maleates; D011955:Receptors, Drug; D011068:Poly G; D012710:Serum Albumin, Bovine; D014700:Verapamil; D003630:Daunorubicin