Targeted Nanoboron Delivery Platform for Boron Neutron Capture Therapy in Refractory Solid Tumors

Abstract: Boron neutron capture therapy (BNCT) represents a promising binary radiotherapy for refractory solid tumors. However, its clinical translation has been historically constrained by the suboptimal pharmacokinetics of conventional boron agents (eg, BPA and BSH), characterized by low tumor selectivity and rapid clearance. This review provides a comprehensive analysis of how nanoengineered delivery platforms—including lipid-based, polymeric, inorganic, and biomimetic nanocarriers—are revolutionizing BNCT. We focus on their advanced targeting mechanisms (passive EPR effect, active ligand/receptor engagement, and nuclear localization), which collectively enable significantly enhanced tumor boron accumulation (T/N ratios of 6– 17) and prolonged intratumoral retention. Furthermore, we critically examine the integration of multimodal imaging techniques (PET, MRI) for real-time dosimetry and treatment planning, which is essential for precision-guided BNCT. Despite remarkable preclinical progress, key translational challenges persist, including the standardization of neutron sources, long-term biocompatibility of nanocarriers, and scalable GMP-compliant manufacturing. In conclusion, the convergence of targeted nanomedicine, precision imaging, and immunomodulation is forging a robust platform. This positions BNCT as an emerging, clinically viable modality within the precision oncology arsenal for refractory malignancies. Keywords: nanodelivery system, boron neutron capture therapy, targeted controlled release, refractory tumors, boron carrier