Enhancing the effectiveness of radiotherapy by targeting tumour metabolism: a microfluidic approach to nanotherapeutic formulation

The work presented within investigated metabolic modulation strategies to enhance tumour cell radiosensitivity by inhibiting the monocarboxylate transporters (MCT1/4) and the mitochondrial pyruvate carrier (MPC), whilst exploring liposomal delivery systems to improve therapeutic efficacy.<br><br>Initial studies demonstrated the radiosensitising potential of MPC inhibition using the small molecule inhibitor 7ACC2.

We report that 7ACC2 altered cell metabolism by reducing oxygen consumption rate (OCR) and increasing extracellular acidification (ECAR). Additionally, we demonstrate enhanced radiosensitivity in both prostate (PC3) and head and neck (FaDu) tumour models, a mechanism underpinned by local reoxygenation. By blocking pyruvate transport, 7ACC2 increased intracellular oxygen availability during radiation, leading to elevated ROS levels and increased DNA double strand break damage.<br><br>Subsequently, we developed a novel liposomal formulation (Lipo-7ACC2) using microfluidics.