Polyethylene glycol complexed with boronophenylalanine as a potential alternative to fructose-boronophenylalanine complexation to increase cellular uptake for BNCT treatment.

Abstract

Objective: Boron Neutron Capture Therapy (BNCT) is a novel precision radiotherapy. The key to BNCT application lies in the effective targeting and retention of the boron-10 (¹⁰B) carrier. Among the various compounds studied in clinical settings, 4-boronophenylalanine (BPA) become the most prevalent one currently. However, challenges such as inadequate solubility and restricted tumor accumulation have affected the clinical efficacy of treatment with BPA. Therefore, there is an urgent need to prepare formulations with higher tumor uptake efficiency and increased intratumoral accumulation.

Methods: polyethylene glycol 400 and BPA were added to methanol and stirred until completely dissolved. The solution was then evaporated to remove methanol, yielding a pale-yellow clear liquid of the PEG400-BPA complex. This complex was then used for in vitro and in vivo experiments, and it was evaluated for inhibition effects after BNCT irradiation in GL261 cells.

Results: Compared to the clinically used fructose-BPA, PEG400-BPA increased the boron uptake in tumor cells nearly twice and exhibited a better tumor-to-normal tissue ratio (T/N) in the in vivo studies. Due to the BNCT efficacy with PEG400-BPA through in vitro experiments, the PEG400-BPA group also had showed significant cell-killing effects.

Conclusion: We discovered that PEG400 can form a complex with BPA, significantly improving its water solubility. It provides a simple, long-term stable, easily convertible, and injectable formulation method for the delivery of BPA in BNCT treatment. It also offers new insights for BPA solubilization and formulation as well as compound forms of administration of boron drugs on the delivery of boron drugs in BNCT.