Fenton reaction-enhanced mild photothermal therapy for cancer suppression with a multifunctional platform

Mild photothermal therapy effectively reduces hyperthermia-related tissue injuries; however, its low therapeutic efficiency presents a significant limitation. Herein, we developed an organic multifunctional photothermal platform with enhanced Fenton catalytic activity to increase tumor sensitivity to mild photothermal therapy. This platform incorporated a self-augmented Fenton molecule integrating carbonic anhydrase inhibitor and ferrocene, which was co-encapsulated with the photothermal agent IR 825 via an amphiphilic polymer. Under near-infrared laser irradiation, IR 825 generated heat for mild photothermal therapy, while the inhibitor blocked carbonic anhydrase IX, resulting in intracellular acidosis due to the H⁺ accumulation. The combination of acidosis and controlled heating facilitated the Fenton reaction, increasing oxidative damage to cells and heightening their sensitivity to heat. Consequently, this synergistic effect enhanced the therapeutic efficacy of mild photothermal therapy against tumor cells, as demonstrated by significant tumor inhibition in our experimental results. This study represents a promising approach towards advancing mild photothermal therapy for cancer treatment.