Water-Soluble closo-Docecaborate-Containing Pteroyl Derivatives Targeting Folate Receptor-Positive Tumors for Boron...

Area of Science:

• Oncology
• Radiochemistry
• Nanomedicine

Background:

• Boron neutron capture therapy (BNCT) requires effective boron delivery agents.
• Folate receptors (FRα) are overexpressed on various cancer cells, making them attractive targets.
• Developing targeted, water-soluble boron carriers is crucial for BNCT advancement.

Purpose of the Study:

• To synthesize and evaluate water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1-4) as novel boron carriers for FRα-targeted BNCT.
• To assess the cytotoxicity, cellular uptake, and targeting mechanism of PBCs in cancer cells.

Main Methods:

• Synthesis of four pteroyl-closo-dodecaborate conjugates (PBCs 1-4).
• In vitro cytotoxicity assays (IC50 determination) against selected human cancer cell lines.
• Cellular uptake studies using FRα-positive and FRα-negative cells.
• Mechanism of uptake investigation via folate competition assays.

Main Results:

• PBCs 1-4 exhibited low cytotoxicity with IC50 values between 1-3 mM, suitable for BNCT agents.
• PBCs 1-3 demonstrated significant cellular uptake in FRα-positive cells, particularly U87MG glioblastoma cells.
• PBC 4 showed lower accumulation compared to PBCs 1-3 and L-BPA.
• Folate competition assays confirmed FRα receptor-mediated endocytosis as the primary uptake mechanism for PBCs 1 and 3.

Conclusions:

• Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs) are promising candidates for FRα-targeted BNCT.
• PBCs 1-3 exhibit favorable characteristics, including low toxicity and specific uptake via FRα.
• Further research into PBCs could lead to improved boron delivery strategies for cancer therapy.