Boron Neutron Capture Therapy at a Crossroads: Translational Gap and Emerging Delivery Agents

The article provides a critical overview of the current status of boron neutron capture therapy (BNCT), highlighting both its therapeutic promise and the challenges limiting its broader clinical translation. BNCT is a binary cancer treatment that combines tumor-selective boron delivery with neutron irradiation to generate highly localized, high-linear-energy-transfer radiation within malignant cells. Although BNCT has shown clinical promise—particularly in glioblastoma and head and neck cancers—its clinical application remains limited. Notably, all human trials to date have relied exclusively on two legacy boron agents: boronophenylalanine (BPA) and sodium borocaptate (BSH). While these compounds enabled early clinical translation, they exhibit significant pharmacological limitations, including suboptimal tumor selectivity, heterogeneous intratumoral distribution, rapid clearance, and formulation challenges.

The review highlights a growing disconnect between chemical innovation and clinical practice. Since 2018, extensive research has produced a diverse range of next-generation boron delivery systems, including modified amino acids, nucleic acid conjugates, porphyrins, carbohydrates, biomimetic compounds, molecular-targeted drugs, and nanocarriers such as polymers, liposomes, and micelles. Many of these platforms demonstrate improved tumor targeting, higher boron payloads, and theranostic capabilities through PET, MRI, or fluorescence imaging, enabling real-time treatment planning and dosimetry.

Despite these advances, none of the new agents have entered clinical trials. The authors identify regulatory barriers, high development costs, limited industrial investment, and the complexity of BNCT (which integrates drug, device, and radiotherapy workflows) as major obstacles to translation. The field now stands at a crossroads: coordinated interdisciplinary collaboration, standardized dosimetry protocols, and stronger academic–industrial partnerships are essential to bridge the translational gap and expand BNCT beyond its historical dependence on BPA and BSH.

Published by Chemistry –A European Journal, 2026
DOI: 10.1002/chem.202503533