Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles

Nanomedicine offers promising strategies for targeted
drug delivery,
imaging, and molecular-level therapies. However, the clinical translation
of nanomedicine has often been hindered by the complex interactions
of nanoparticles (NPs) with biological systems. This study investigates
a cell-based delivery platform designed to overcome some of these
limitations, using clinical-grade tumor-infiltrating lymphocytes (TILs)
as biological carriers of boron carbide (B4C) NPs in boron
neutron capture therapy (BNCT). Biological vectors, such as TILs,
could enable selective tumor targeting, leading to highly localized 10B levels and minimizing off-target accumulation. We evaluated
the uptake and retention of composite Fe2O3–B4C NPs (FeBNPs) using both immortalized Jurkat T cells and
primary human TILs. Both cell types efficiently internalized FeBNPs
without cytotoxic effects, maintained their functionalities, and retained
the boron-rich NPs for up to 72 h. Imaging confirmed intracellular
localization, and neutron autoradiography demonstrated that TILs accumulated
sufficient 10B for therapeutic efficacy, eliminating the
need for isotopically enriched compounds like L-4-boronophenylalanine
(BPA) or sodium borocaptate (BSH). Coculture experiments with Jurkat
and HeLa cells confirmed that lymphocyte-delivered boron could mediate
localized radiation damage via neutron capture. These findings support
the concept of TILs as “Trojan Horses” for boron delivery,
allowing for overcoming traditional barriers in NP-based therapies
and taking advantage of their innate tumor-homing ability. This approach
not only enhances BNCT selectivity and efficacy but also supports
the integration of nanomedicine with adoptive cell therapy in a combined
cancer treatment framework.