124I-radiolabeled Exosome-Based Treatment Platform for Enhanced Boron Neutron Capture Therapy: Precise Delivery and Real-Time PET Tracking of Boron

Abstract

Boron neutron capture therapy (BNCT) is a promising targeted radiotherapy modality, whose efficacy critically depends on the precise spatiotemporal synchronization of sufficient boron accumulation in tumor cells with neutron irradiation. To achieve this coordination, we developed an integrated treatment platform based on exosome-delivered ¹⁰B-containing carbon dots (BCDs), which allows tracking via positron emission tomography (PET) imaging. We first established a screening system focusing on various key parameters, including blood-brain barrier (BBB) permeability, glioma-targeting specificity, and the coating rate of exosomes on BCDs. Through systematic screening, mouse plasma-derived exosomes (Mouse-Exo) were identified as the optimal carrier, exhibiting superior BBB permeability and glioma-targeting specificity. Isothermal titration calorimetry confirmed that the coating of exosomes on BCDs is driven by spontaneous electrostatic interactions. The Exo-BCDs delivery system showed a significantly prolonged circulation half-life and achieved a tumor boron concentration of 123.44 ng/10⁶ cells. That is approximately 6.17 times the therapeutic threshold, significantly enhancing tumor cell killing in BNCT. To elegantly resolve the inherent conflict between the high boron dose required for therapy and the low tracer dose sufficient for PET imaging, we propose a strategy of doping a small amount of ¹²⁴I-labeled BCDs into a large excess of unlabeled BCDs, followed by exosome encapsulation. This approach offers a practical and clinically translatable strategy for real-time treatment guidance. This study provides a generalizable technical paradigm for advancing exosome-mediated BNCT toward clinical application in glioma.