Targeting adriamycin to tumour cells by means of an affinity ligand; a model system for drug delivery.
Actively migrating tumour cells possess the proteolytic enzyme guanidinobenzoatase (GB) in an uninhibited form. This enzyme has been used as a target for the delivery of adriamycin to invasive tumour cells in frozen sections. An adriamycin-agmatine complex has been prepared which act as a competitive inhibitor of GB. Competition experiments have demonstrated that the adriamycin-agmatine complex competes with 9-aminoacridine for the active centre of GB associated with invasive tumour cells, located in the lymph nodes and in squamous cell carcinoma of the oral cavity. The technique described should be generally applicable to the targeting of drugs to cells.
Steven
F S
FS
Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Manchester, U.K.
Griffin
M M
MM
Williams
L A
LA
Ali
H
H
Maier
H
H
D000376:Agmatine / Q000008:administration & dosage*; D000585:Aminacrine / Q000378:metabolism; D001667:Binding, Competitive; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D010450:Endopeptidases; D005453:Fluorescence; D006146:Guanidines / Q000008:administration & dosage*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008207:Lymphatic Metastasis
D004337:Drug Carriers; D006146:Guanidines; D008024:Ligands; D000376:Agmatine; D000585:Aminacrine; D004317:Doxorubicin; D002265:Carboxylic Ester Hydrolases; C037288:guanidinobenzoate esterase; D010450:Endopeptidases