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Folate targeting is a method utilized in biotechnology for drug delivery purposes. This Trojan Horse process, which was created by Drs. Christopher P. Leamon and Philip S. Low, involves the attachment of the vitamin, folate (folic acid), to a molecule/drug to form a "folate conjugate". Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates also bind tightly to the FR and trigger cellular uptake via endocytosis. Molecules as diverse as small radiodiagnostic imaging agents to large DNA plasmid formulations have successfully been delivered inside FR-positive cells and tissues. ==Background== Folic acid (FA, folate or vitamin B9), is a vital nutrient required by all living cells for nucleotide biosynthesis and for the proper metabolic maintenance of 1-carbon pathways. Aside from its cofactor role for intracellular enzymes, FA also displays high affinity for the folate receptor (FR), a glycosylphosphatidyinositol-linked protein that captures its ligands from the extracellular milieu and transports them inside the cell via a non-destructive, recycling endosomal pathway. The FR is also a recognized tumor antigen/biomarker.〔 〕 Because of this, diagnostic and therapeutic methods which exploit the FR’s function are being developed for cancer. The FR is an emerging therapeutic target for diagnosis and treatment of cancer and chronic inflammatory diseases. Expression of the FR is selectively upregulated on certain malignant cells and activated macrophages. Overexpression of the FR on these types of cells is clinically significant because they designate areas where the physiological symptoms of disease are most extensive. The malignant cells indicate the presence of tumors associated with ovarian, lung, breast, kidney, brain, endometrial, and colon cancer. Macrophages become activated in chronic diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, atherosclerosis, diabetes, and most other inflammatory diseases.〔 From a mechanistic perspective, the FR functions to concentrate exogenous ligands (e.g. folates and folate-drug conjugates) into the cell cytosol by endocytosis.〔 The term endocytosis refers to the process whereby the plasma membrane invaginates and eventually forms a distinct intracellular compartment. The endocytic vesicles (endosomes) rapidly become acidified to allow the FR to release its ligand. Afterwards, the empty FR returns to the cell surface where it can participate in another round of ligand-mediated endocytosis. The discovery of vitamin-mediated drug targeting in plants led to the hypothesis that folate-targeted therapies could be of clinical use.〔 After proteins covalently bonded to biotin were successfully transported into plant cells through receptor-mediated endocytosis, a similar technique was attempted with folate and animal cells.〔 Targeted drug therapy is advantageous because it deposits the drug at the specific location where it can be most useful in treating the disease. Similarly, folate-targeted imaging therapy helps visualize areas where the FR is expressed at higher levels. With greater control over where exogenous agents are delivered, diagnostic and treatment therapies are more effective and cause fewer side effects. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Folate targeting」の詳細全文を読む スポンサード リンク
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