Orbital coupling nanozymes with enhanced peroxidase-like activity mediate deep thermal ablation/chemodynamic therapy to boost immune response

Developing nanozymes with efficient peroxidase-like activity while overcoming the limitations of single nanozyme therapy to enhance therapeutic effects is a great challenge for cancer chemodynamic therapy. Herein, we developed PtSn nanozymes with enhanced peroxidase-like activity and outstanding photothermal properties as nanomedicines for cancer treatment. Firstly, the orbital coupling in PtSn nanozymes can optimize the d-band center, thereby promoting enhanced peroxidase-like activity, which can specifically activate H ₂ O ₂ to generate highly toxic hydroxyl radical. Meanwhile, PtSn nanozymes can absorb light in the second near-infrared region (1000–1500 nm) and convert it into effective thermal energy, exhibiting excellent photothermal effects (η = 43.85%) and good photothermal stability, which can effectively kill deep tumor tissues. Notably, the temperature of photothermal therapy can simultaneously enhance the peroxidase-like activity efficiency of PtSn nanozymes to produce more reactive oxygen species, further enhancing the anti-tumor effect of the nanozymes. Furthermore, immunological studies have found that the chemodynamic/photothermal synergistic strategy enhances the maturation of dendritic cells and the activation of T cells, while simultaneously reducing the number of immunosuppressive cells (MDSCs), thereby reducing the incidence of distant metastases and lung metastases. Therefore, PtSn nanozymes can autonomously implement the chemodynamic/photothermal-immunotherapy synergistic strategy, achieving a “three-in-one” therapeutic effect in tumor treatment.