Water-Soluble closo-Docecaborate-Containing Pteroyl Derivatives Targeting Folate Receptor-Positive Tumors for Boron Neutron Capture Therapy

Authors:   Nakagawa F., Kawashima H., Morita T., Nakamura H.
Journal: Cells
https://doi.org/10.3390/cells9071615
Abstract: Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1–4), were developed as folate receptor (FR?) targeting boron carriers for boron neutron capture therapy (BNCT). PBCs 1–4 had adequately low cytotoxicity with IC50 values in the range of 1~3 mM toward selected human cancer cells, low enough to use as BNCT boron agents. PBCs 1–3 showed significant cell uptake by FR? positive cells, especially U87MG glioblastoma cells, although the accumulation of PBC 4 was low compared with PBCs 1–3 and L-4-boronophenylalanine (L-BPA). The cellular uptake of PBC 1 and PBC 3 by HeLa cells was arrested by increasing the concentration of folate in the medium, indicating that the major uptake mechanisms of PBC 1–3 are primarily through FR? receptor-mediated endocytosis.