Journal
JOURNAL OF DRUG TARGETING
Volume 21, Issue 5, Pages 458-465Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/1061186X.2013.765441
Keywords
AFP receptor; alpha-fetoprotein; drug targeting; receptor-mediated endocytosis; recombinant protein
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Funding
- Russian Foundation for Basic Research (RFBR) (Russian Federation) [10-04-015-79]
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The alpha-fetoprotein (AFP) binding protein, a putative AFP receptor, is a tumour marker that is present on the surfaces of malignant cells. AFP enters cells through receptor-mediated endocytosis. The recombinant C-terminal fragment of AFP (AFP-3BC, which consists of amino acid residues 473-596) was obtained by the expression in Escherichia coli. AFP-3BC was shown to be bound specifically to the AFP putative receptor on tumour cells and accumulated by endocytosis in these cells in a similar manner to that of full-length human AFP. In lymphocytes, the binding and endocytosis of AFP-3BC were absent. Thus, the AFP receptor binding site was shown experimentally to be located within the AFP-3BC sequence. A conjugate of synthesised AFP-3BC with the antitumour antibiotic doxorubicin (DOX-AFP-3BC) demonstrated high antitumour activity in vitro. Thus, AFP-3BC can be used successfully as a vector for the targeted selective delivery of drugs into tumour cells.
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