A Platelet-Mimicking Single-Atom Nanozyme for Mitochondrial Damage-Mediated Mild-Temperature Photothermal Therapy.

Single-atom nanozyme (SAzyme) systems have shown great potential in tumor therapy. A multifunctional SAzyme not only possesses high catalytic activity but also can be used as photothermal agents in photothermal therapy (PTT). Furthermore, it is also imperative to overcome tumor thermal resistance in SAzyme-based PTT so that PTT under a mild temperature is achievable. Herein, a novel platelet membrane (PM)-coated mesoporous Fe single-atom nanozyme (Fe-SAzyme) was formulated to solve these issues. The PM-coated mesoporous Fe-SAzyme (PMS) showed a satisfactory NIR-II photothermal performance, high peroxidase (POD) activity, and good tumor-targeting ability. In addition, PMS may be used as a carrier for protein drugs owing to its inner mesoporous structure. In vitro experiments showed that PMS could inhibit the expression of heat shock protein (HSP) by damaging the mitochondria, thereby finally improving the effect of mild-temperature PTT. Moreover, in vivo results showed that PMS could efficiently accumulate in tumor sites and suppress tumor growth with minimal toxicity in major organs. To the best of our knowledge, this study is the first report of a biomimetic mesoporous Fe-SAzyme used to achieve mitochondrial damage-mediated mild-temperature PTT. The study provides new promising ideas for designing other SAzyme systems for cancer treatment.