A gadolinium-doped polyphenol-boron nanodrug for improved boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a promising strategy for selective tumor eradication. However, the clinical application of the boron delivery agent p‑boronophenylalanine (BPA) is limited by challenges such as poor solubility, suboptimal tumor accumulation, and lack of effective imaging capabilities. Here, we present a metal polyphenol-based boron nanodrug (EB@Gd NPs), designed to address these challenges and enhance the efficacy of BNCT. Self-assembled from epigallocatechin-3-gallate (EGCG), BPA, and gadolinium ions (Gd³⁺), the EB@Gd NPs exhibit significantly improved tumor targeting and enable real-time magnetic resonance imaging (MRI). These nanoparticles show enhanced tumor accumulation, with MRI providing dynamic insights into boron distribution, thus aiding in determining optimal timing for neutron irradiation. Furthermore, EGCG potentiates therapeutic effect of BNCT by inhibiting DNA repair and promoting efficient DNA double-strand breaks. Therefore, the EB@Gd NPs demonstrate potent tumor growth inhibition in BNCT, holding great potential for improving precision and efficacy of BNCT in cancer therapy.