Enhancing photothermal therapy effectiveness via tartrazine-induced optical clearing of biological tissues

Photothermal therapies offer a powerful strategy for noninvasive treatment of cancer and other pathological conditions by converting light energy into localized heat to ablate diseased tissues or induce local release of antigens. However, the efficacy and precision of these therapies are severely restricted by optical scattering in biological tissues, which limits light penetration and spatial accuracy in vivo. In this work, we leverage the food coloring dye tartrazine-a strongly absorbing molecule in UV-VIS range ([Formula: see text]250 nm and [Formula: see text]430 nm) and with minimal absorption over 600 nm-to reduce tissue scattering and thereby enhance the delivery and efficacy of photothermal treatment. We demonstrate that when in aqueous environments, tartrazine induces local refractive index changes and minimizes the mismatch between water-based environments and lipid-rich tissue components, leading to a scattering reduction up to [Formula: see text]65% and enabling deeper light penetration and more homogeneous energy delivery. By incubating 3D samples with the dye, we achieved reversible optical clearing in ex vivo tissues, allowing near-complete light transmission through otherwise opaque sections. The enhanced optical accessibility directly improves the spatial resolution and energy deposition of photothermal therapies, potentially reducing off-target effects and tissue damage. Our results introduce a complementary perspective in photothermal therapy optimization, emphasizing that molecular absorption can play a central role beyond conventional thermal efficiency considerations. This refractive index-modulation opens the door to more targeted, efficient, and safe photothermal treatment protocols and offers a generalizable framework for light-based therapeutic applications in living organisms.