单原子纳米酶（Single-atom nanozymes，简称SAzymes）为发展具有催化活性与天然过氧化物酶（peroxidase，简称POD）相媲美的人工酶打开了新的可能性。迄今为止，大部分研究都集中在结构调控Fe-N4基团，以模拟金属蛋白血红素中心。然而，结构复杂的非血红素铁过氧化物酶（non-heme-iron POD），如HppE，尚未成功模拟。在本研究中，我们通过利用碳点（carbon dots，简称CDs）中无序的亚纳米级区域，合成了具有扭曲的非平面式Fe-O3N2活性位点的Fe-CDs-SAzymes，与HppE中的非血红素铁中心相似度极高。Fe-CDs表现出出色的POD活性，达到750个单位/毫克，超过了具有平面式Fe-N4的常规SAzymes。我们进一步制备了一种活化的Fe-CDs基治疗剂，具有近红外增强的POD活性、光热效应和靶向肿瘤能力。我们的研究结果在高性能SAzymes的设计中迈出了重要一步，并为未来的协同抗肿瘤疗法提供了指导。

Single-atom nanozymes (SAzymes) open new possibilities for the development of artificial enzymes that have catalytic activity comparable to that of natural peroxidase (POD). So far, most efforts have focused on the structural modulation of the Fe-N4 moiety to mimic the metalloprotein heme center. However, non-heme-iron POD with much higher activity, for example, HppE, has not been mimicked successfully due to its structural complexity. Herein, carbon dots (CDs)-supported SAzymes with twisted, nonplanar Fe-O3N2 active sites, highly similar to the non-heme iron center of HppE, was synthesized by exploiting disordered and subnanoscale domains in CDs. The Fe-CDs exhibit an excellent POD activity of 750 units/mg, surpassing the values of conventional SAzymes with planar Fe-N4. We further fabricated an activatable Fe-CDs-based therapeutic agent with near-infrared enhanced POD activity, a photothermal effect, and tumor-targeting ability. Our results represent a big step in the design of high-performance SAzymes and provide guidance for future applications for synergistic tumor therapy.