A pH-responsive single-atom nanozyme for photothermal-augmented nanocatalytic tumor therapy

Based on the physiological conditions of the tumor microenvironment (TME), many effective therapeutic strategies have been reported by using nanocatalysts. The main challenge is the insufficient catalytic activity of nanocatalysts within the acidic TME, significantly constraining their therapeutic efficacy. Herein, a pHresponsive bifunctional platform is developed with multiple enzyme-like catalytic activities for synergistic tumor therapy by integrating Rh single atoms nanozymes (SA-Rh nanozymes) with photothermal therapy (PTT). The SA-Rh nanozymes display peroxidase-mimicking activities within tumor cells, inducing a synergistic effect of enhanced reactive oxygen species generation for collaborative cancer therapy involving both chemodynamic therapy and PTT. Additionally, SA-Rh nanozymes exhibit catalase mimicking activities, enabling the generation of oxygen, and facilitating efficient nanozyme catalytic therapy in a substrate-cycle manner. Moreover, the catalytic efficiency of SA-Rh nanozymes is found to be higher under weak acidic conditions (pH=6.0) compared to neutral conditions (pH=7.4), thereby enabling the maintenance of catalytic activity in an acidic environment. The incorporation of this feature enhances its catalytic activity within the TME, optimizing the efficacy of nanozyme. The remarkable near-infrared I region absorption capability confers SA-Rh nanozymes with exceptional PTT performance, achieving an impressive efficiency of 34.1 %. Therefore, the SA-Rh nanozymes exhibit a remarkable ability to induce apoptosis in cancer cells through synergistic CDT and PTT modalities, effectively overcoming the shortcomings of current nanozyme catalytic therapy.