Vitamin B12-mediated transport: a potential tool for tumor targeting of antineoplastic drugs and imaging agents.
The uptake of vitamin B12 (cyanocobalamin, Cbl/VB12) in mammalian cells is mediated by specific, high-affinity receptors for the vitamin B12-binding protein, transcobalamin II, which is expressed on the plasma membrane. The receptor for vitamin B12 is overexpressed on a number of human tumors, including cancers of the ovary, kidney, uterus, testis, brain, colon, lung, and myelocytic blood cells. Furthermore, the affinity of cyanocobalamin conjugates for cell surface transcobalamin II receptors seems to be high enough so that vitamin B12 derivatization with the cytotoxic agent or carriers bearing cytotoxic drugs allows the selective delivery of diagnostic and therapeutic agents to cancer cells. Thus, conjugates of vitamin B12 enter receptor-expressing cancer cells via receptor-mediated endocytosis, and targeting may be accomplished by multiple mechanisms, depending on the drug-delivery strategy. This review summarizes the applications of vitamin B12 as a targeting ligand and highlights the various methods being developed for delivery of therapeutic and imaging agents to cancer cells in vitro and in vivo. This review reflects the potentiality of vitamin B12 for tumor targeting of chemotherapeutic and diagnostic agents.
Gupta
Yashwant
Y
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar (M.P.) 470 003, India.
Kohli
Dharm Veer
DV
Jain
Sanjay K
SK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003078:Colchicine / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D014155:Transcobalamins / Q000276:immunology / Q000378:metabolism*; D014805:Vitamin B 12 / Q000737:chemistry / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D014155:Transcobalamins; D014805:Vitamin B 12; D003078:Colchicine