Spatial Targeting of Sialic Acid Receptors for MRI/BNCT-Integrated Boron Drug-Based Antitumor Therapy

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