Molecules as diverse as small radiodiagnostic imaging agents to large DNA plasmid formulations have successfully been delivered inside FR-positive cells and tissues.
[2][3] 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.
[4] Aside from its cofactor role for intracellular enzymes, FA also displays high affinity for the folate receptor (FR), a glycosylphosphatidylinositol-linked protein that captures its ligands from the extracellular milieu and transports them inside the cell via a non-destructive, recycling endosomal pathway.
The malignant cells indicate the presence of tumors associated with ovarian, lung, breast, kidney, brain, endometrial, and colon cancer.
[12] From a mechanistic perspective, the FR functions to concentrate exogenous ligands (e.g. folates and folate-drug conjugates) into the cell cytosol by endocytosis.
Folate is attached to polyethylene glycol bound to the phosphate heads of membrane phospholipids, thus directing the liposomes to FRs of tumor cells, by which they are engulfed.
[26][27] Taken together, the total number of tumors that express the FR is very large; therefore, FR-targeted strategies could have significant impact on cancer treatment for patients diagnosed with FR-positive disease.
It is a molecule constructed with a single FA moiety and extended by a hydrophilic peptide-based spacer that is, in turn, linked to Vinca alkaloid and mitomycin units via 2 distinct disulfide-containing linkers.
[29] Animals bearing well-established human tumor xenografts were found to completely respond to EC0225 therapy with dosing regimens that were approximately 3-fold less intensive to that required for EC145.
By reducing hepatic clearance, less drug will transit through the biliary excretion route; as a consequence, less off-target toxicities (predicted from preclinical tests) are expected.
Normally, they circulate in the bloodstream in a dormant state, but at a site of inflammation due to injury or autoimmune disease, they become activated, changing shape and expressing different cell surface markers.
[39] It is expected that ailments which harbor activated macrophages (such as arthritis, psoriasis and inflammatory bowel disease) may someday be treatable with folate-targeted medicines.