Abstract

Objective Boron neutron capture therapy (BNCT) is limited by inadequate boron delivery to tumor cells and the inability to visualize boron agents for personalized treatment. This study introduces DOTA-BPA-Gd, a dual-function boron agent integrating BNCT efficacy with drug tracing. Methods DOTA-BPA-Gd was designed with four phenylboronic acid groups to target sialic acid residues on cancer cell surfaces. This strategy aims to enhance tumor boron accumulation while avoiding LAT1-mediated exocytosis and transporter saturation associated with BPA-F. With a molecular weight of ~ 1200 Da, DOTA-BPA-Gd allows efficient spatial binding to sialic acid, improving targeting specificity. Cellular uptake, cytotoxicity, and boron distribution were evaluated, followed by in vivo BNCT experiments with MRI monitoring. Results DOTA-BPA-Gd effectively delivered boron to cancer cells without detectable toxicity. Under neutron irradiation, the DOTA-BPA-Gd + N group showed significant tumor inhibition, with tumor volumes reduced to about one-third of those in the BPA-F + N group. Furthermore, gadolinium enabled real-time MRI-based tracking of boron biodistribution, confirming the agent’s dual functionality. Conclusions DOTA-BPA-Gd offers a promising strategy for BNCT by combining targeted boron delivery with non-invasive imaging. This integrated approach improves treatment precision, enhances therapeutic efficacy, and may help overcome key clinical challenges in BNCT. Graphical