Poly(vinyl alcohol) enhancing therapeutic effects of 4-l-boronophenylalanine on thoracic tumors in neutron capture therapy

Boron neutron capture therapy (BNCT) has been expected to be a promising approach to treat lung cancers in a non-invasive manner. Development of boron drugs showing efficient accumulation and long-term retention within the target tumor is key to realizing BNCT for such deep-seated cancers. Here, we report that the complex comprising poly(vinyl alcohol) (PVA) and 4-l-boronophenylalanine (BPA), the only clinically approved drug in BNCT, could show drastic therapeutic efficiency to thoracic tumors mimicking intractable malignant pleural mesothelioma (MPM) in mice. We first optimized the preparation method and composition of the formulation with the aid of sorbitol as a solubilizer. The optimized formulation termed PVA-sorbitol-BPA exhibited dramatical reduction of possible side effects to ignorable levels in comparison with the prototype of PVA-BPA complexes. Systemically administered PVA-sorbitol-BPA showed efficient accumulation and long-term retention within the target tumor. BNCT with PVA-sorbitol-BPA significantly improved survival rates even compared with conventional BPA. Our results indicate that PVA may be a promising additive to boost the therapeutic potential of BPA for treatment of tumors in the torso, expanding the indications for BNCT.