Boron delivery agents in BNCT: A mini review of current developments and emerging trends

Boron Neutron Capture Therapy (BNCT) is a highly targeted form of radiation therapy offering significant potential for treating hard-to-manage cancers such as glioblastoma, head and neck cancer, and recurrent melanoma [1]. Its effectiveness relies on the selective accumulation of boron-10 within tumor cells, enabling localized high-linear-energy transfer (high-LET) damage through neutron capture reactions. Despite the promise of this therapeutic approach, the development of efficient boron delivery agents remains a critical challenge. This review explores the evolution of boron delivery agents over three generations, highlighting their advancements, limitations, and emerging trends. Early first-generation agents, such as sodium tetraborate, faced issues with tumor specificity and retention, leading to the introduction of second-generation agents like boronophenylalanine (BPA) and sodium borocaptate (BSH). While these agents improved therapeutic outcomes, they exhibited limitations in tumor uptake mechanisms, selectivity, and retention. Recent advancements have resulted in third-generation agents that integrate nanotechnology, monoclonal antibodies, and multifunctional frameworks, significantly enhancing tumor specificity and therapeutic efficiency. These innovative agents utilize targeted delivery, imaging capabilities, and theranostic functionalities to optimize treatment outcomes. However, challenges remain in overcoming tumor heterogeneity, ensuring regulatory compliance, and scaling up production. This review provides a comprehensive analysis of current developments in boron delivery systems, offering insights into their potential to transform BNCT into a more effective and accessible cancer therapy.