Abstract
Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1–4), were developed as folate receptor (FRα) 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 FRα 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 FRα receptor-mediated endocytosis.
Highlights
Boron neutron capture therapy (BNCT) has been attracting attention as a noninvasive radiotherapy in cancer treatment
It is known that L-BPA is actively accumulated into cancer cells through L-type amino acid transporter 1 (LAT-1) [12,13], which is overexpressed in many cancer cells
pteroyl-closo-dodecaborate conjugates (PBCs) 1–4 have adequately low cytotoxicity with IC50 values in the range of 1~3 mM toward these human cancer cells, low enough to use as BNCT boron agents
Summary
Boron neutron capture therapy (BNCT) has been attracting attention as a noninvasive radiotherapy in cancer treatment. The combination of boron agents with sufficient and selective accumulation of 10 B in cancer cells and an appropriate neutron source is essential for successful cancer treatment with BNCT [1,2]. Accelerator-based thermal neutron generators for BNCT have been developed worldwide [3,4,5,6,7,8,9,10], and one was approved in Japan this year as a medical device [6,7] in combination with L-4-boronophenylalanine (L-BPA) [11] for the treatment of head and neck carcinoma patients.
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