Cold Exposure Therapy Enhances Single-Atom Nanozyme-Mediated Cancer Vaccine Therapy

Single-atom nanozymes are highly effective in the preparation of tumor vaccines (TV) due to their superior peroxidase (POD) activity and excellent biocompatibility. However, the immunosuppressive environment within tumors can diminish the efficacy of these vaccines. Cold exposure (CE) therapy, a noninvasive and straightforward antitumor method, not only suppresses tumor metabolism but also ameliorates the immunosuppressive tumor milieu. In this study, we developed personalized TV using copper single-atom nanozyme (Cu SAZ) and enhanced their long-term antitumor efficacy by introducing CE. We initially synthesized the Cu SAZ via high-temperature carbonization, which demonstrated robust POD activity and photothermal characteristics. Upon exposure to 808 nm laser irradiation, the nanozyme generated reactive oxygen species (ROS) and heat, inducing immunogenic cell death in 4T1 breast cancer cells or CT26 colon cancer cells and facilitating TV production. In our <i>in vivo</i> tumor prevention and treatment model, we noted that CE significantly boosted the efficacy of the TV. The primary mechanism involves CE's ability to lower the ratio of myeloid-derived suppressor cells (MDSCs), decrease glucose metabolism in tumor cells, and increase the proportions of CD8⁺ T cells and memory T cells. Collectively, our findings offer promising avenues for designing innovative TV systems.