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Vitamin-mediated Targeting As A Potential Mechanism To Increase Drug Uptake By Tumours.

G. Russell-Jones, K. McTavish, J. McEwan, J. Rice, D. Nowotnik
Published 2004 · Medicine, Chemistry

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Targeted chemotherapy for cancer treatment offers a great potential advantage in tumour treatment due to greater specificity of delivery which leads to increased dose of the cytotoxin delivered to the tumour relative to the rest of the body. In order to achieve such selective targeted delivery one needs to identify generic markers that are over-expressed on the surface of tumour cells but are not over-expressed on normal tissue. Work of several authors has shown that some cells, such as those of rapidly dividing, aggressive tumours, over-express surface receptors involved in the uptake of vitamin B(12) [B. Rachmilewitz, M. Rachmilewitz, B. Moshkowitz, J. Gross, J. Lab. Clin. Med. 78 (1971) 275-279; B. Rachmilewitz, A. Sulkes, M. Rachmilewitz, A. Fuks, Israel J. Med. Sci. 17 (1981) 874-879] or folate [P. Garin-Chesa, I. Campbell, P.E. Saigo, J.L. Lewis Jr., L.J. Old, W.J. Rettig, Am. J. Pathol. 142 (1993) 557-567; O.C. Boerman, C.C. van Niekerk, K. Makkink, T.G.J.M. Hanselaar, P. Kenemans, L.G. Poels, Int. J. Gynecol. Pathol. 10 (1991) 15-25; G. Toffoli, C. Cernigoi, A. Russo, A. Gallo, M. Bagnoli, M. Boiocchi, Int. J. Cancer 74 (1997) 193-194; J.A. Reddy, D. Dean, M.D. Kennedy, P.S. Low, J. Pharm. Sci. 88 (1999) 1112-1118; J.A. Reddy, P.S. Low, Crit. Rev. Ther. Drug Carrier Syst. 15 (1998) 587-627; G.J. Russell-Jones, K. McTavish, J.F. McEwan, in: Proceedings of the 2nd International Symposium on Tumor Targeted Delivery Systems, 2002]. Furthermore the degree of over-expression has been found to correlate with the stage of tumour growth, with the highest levels found on stage IV carcinomas. Using fluorescently-labelled polymers to which are linked the targeting agents, vitamin B(12), folate or biotin, the relative uptake of these polymers into various types of tumour cell lines grown both in vitro and in vivo has been examined. These studies have shown that while some tumour types do NOT over-express receptors involved in vitamin uptake, most tumour types over-express receptors for folate, or vitamin B(12). In either case there is also a greatly increased expression of a yet to be identified biotin receptor. In cases of receptor over-expression, binding of the targeted fluorochrome leads to rapid internalization of these molecules within the cells to levels that are two to thirty times higher than with non-targeted polymers. Using a number of cancer models, these studies were extended further and it was found that the increased expression of receptors also leads to increased levels of killing with targeted cytotoxins. Thus the preliminary data described suggests that the use of vitamins as targeting agents has enormous potential for use in cancer diagnosis and chemotherapy.
This paper references
Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression.
S. Gottschalk (1994)
Antibodies to Transcobalamin II Block In Vitro Proliferation of Leukemic Cells
G. R. McLean (1997)
Biodistribution of radiolabeled adenosylcobalamin in patients diagnosed with various malignancies.
D. Collins (2000)
Folate-mediated targeting of antineoplastic drugs, imaging agents, and nucleic acids to cancer cells.
S. Wang (1998)
Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis.
C. P. Leamon (1991)
Transcobalamin II receptor imaging via radiolabeled diethylene-triaminepentaacetate cobalamin analogs.
D. Collins (1997)
Synthesis, purification, and tumor cell uptake of 67Ga-deferoxamine--folate, a potential radiopharmaceutical for tumor imaging.
S. Wang (1996)
Transcobalamin II and in vitro proliferation of leukemic cells.
G. R. McLean (1998)
Comparative Immunohistochemical Study of Four Monoclonal Antibodies Directed Against Ovarian Carcinoma‐Associated Antigens
O. Boerman (1991)
Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein.
P. Garinchesa (1993)
Expression of folate binding protein as a prognostic factor for response to platinum‐containing chemotherapy and survival in human ovarian cancer
G. Toffoli (1998)
Synthesis of [(99m)Tc]DTPA-folate and its evaluation as a folate-receptor-targeted radiopharmaceutical.
C. Mathias (2000)
Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor.
E. C. Wiener (1997)
Folate-mediated targeting of therapeutic and imaging agents to cancers.
J. Reddy (1998)
A kit formulation for preparation of [(111)In]In-DTPA-folate, a folate-receptor-targeted radiopharmaceutical.
C. Mathias (1998)
Accumulation of labelled vitamin B12 in some transplanted tumours
H. Flodh (1968)
Synthesis and nca-radioiodination of arylstannyl-cobalamin conjugates. Evaluation of aryliodo-cobalamin conjugate binding to transcobalamin II and biodistribution in mice.
D. Wilbur (1996)
Optimization of folate-conjugated liposomal vectors for folate receptor-mediated gene therapy.
J. Reddy (1999)
Uptake and distribution of fluorescently labeled cobalamin in neoplastic and healthy breast tissue
M. Cannon (2000)
Serum transcobalamin in myeloid leukemia.
B. Rachmilewitz (1971)
Chimeric murine-human antibodies directed against folate binding receptor are efficient mediators of ovarian carcinoma cell killing.
L. Coney (1994)
Single-chain Fv/folate conjugates mediate efficient lysis of folate-receptor-positive tumor cells.
B. K. Cho (1997)
Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein.
L. Coney (1991)
Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical.
S. Wang (1997)
Tumor imaging via indium 111-labeled DTPA-adenosylcobalamin.
D. Collins (1999)
Endocytosis of folate-protein conjugates: ultrastructural localization in KB cells.
J. Turek (1993)
Overexpression of folate binding protein in ovarian cancers
G. Toffoli (1997)
Cobalamin analogues modulate the growth of leukemia cells in vitro.
G. R. McLean (1997)
99mTc-ethylenedicysteine-folate: a new tumor imaging agent. Synthesis, labeling and evaluation in animals.
S. Ilgan (1998)
99mTc-HYNIC-folate: a novel receptor-based targeted radiopharmaceutical for tumor imaging.
W. Guo (1999)
Folate-mediated targeting: from diagnostics to drug and gene delivery.
C. P. Leamon (2001)
Enhanced folate receptor mediated gene therapy using a novel pH-sensitive lipid formulation.
J. Reddy (2000)
Imaging tumor folate receptors using 111In-DTPA-methotrexate.
S. Ilgan (1998)
Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues.
S. Weitman (1992)

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