Biomimetic nanozyme mitigates thermal damage in photothermal therapy by targeted disruption of tumor metabolism.

Thermal damage to surrounding healthy tissues poses a challenge in photothermal therapy (PTT) due to the limited targeting efficiency. Here, we report the development of the membrane-functionalized low-temperature photothermal nanozymes M@Au@ZPC (MAZ), thereby mitigating the adverse effects of thermal spillage through simultaneously increasing targeting distribution and decreasing photothermal temperature. The coating of the tumor cell membrane significantly enhanced the accumulation of MAZ at the target site by exploiting the homologous targeting capability of membranes. Furthermore, the catalytic consumption of glucose by Au nanozymes at the tumor site results in the inhibition of ATP production within tumor cells, which subsequently downregulates the expression of heat shock proteins, significantly diminishing the thermotolerance of the tumor cells. As a result, tumor ablation can be effectively achieved at lower temperatures, thereby minimizing the potential for thermal damage. Both in vitro and in vivo experimental results indicated that MAZ nanoparticles can facilitate tumor ablation through targeted low-temperature photothermal therapy. This study informs new therapeutic strategies to decrease adverse effects of thermal spillage in PTT.