Nanomedicine has long promised highly selective cancer treatments, yet its clinical success remains limited by poor tumor targeting and unpredictable interactions with biological systems.

Boron Neutron Capture Therapy (BNCT) is a form of radiotherapy that relies on the selective accumulation of boron in the tumor mass, which, upon neutron irradiation, releases high-energy particles capable of destroying cancer cells with minimal damage to healthy tissue. However, despite several attempts to enhance BNCT efficacy through nanomedicine-based delivery systems, these strategies have failed to achieve efficient and specific boron delivery to tumors.

To overcome this, we repurpose tumor-infiltrating lymphocytes (TILs), immune cells that naturally home to tumors, as living carriers for boron-based nanoparticles, enabling a targeted and biologically compatible delivery platform. We demonstrate that both Jurkat T cells and patient-derived TILs can efficiently internalize iron oxide-boron carbide nanoparticles while preserving their viability and immune function, retaining therapeutic boron levels for up to 72 hours. Imaging and autoradiography confirm intracellular nanoparticle retention and sufficient boron delivery for effective neutron capture therapy.

Co-culture experiments with cancer cells confirmed that lymphocyte-delivered boron could mediate localized radiation damage via neutron capture. By turning TILs into “Trojan horses,” our approach merges adoptive cell therapy with nanomedicine, enhancing tumor selectivity and bypassing key delivery hurdles. These findings are further validated in advanced cancer-on-a-chip models, paving the way for smarter, cell-guided radiotherapies.