Fe−O−Mo Site‐Activated Nanozymes for Bienzymatic/Upconversion Synergistic Catalytic Anticancer Therapy

作者：Qiang Wang, Shuang Liu, Chunsheng Li, Yaru Huang, Boqi An, Meng Wang, Jiawei Qu, Peiyao Wang, Jiating Xu, Ping’an Ma · 发表于：Angewandte Chemie International Edition · 年份：2025 · DOI：10.1002/anie.202511471 · 被引用次数：21 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Nanocluster Synthesis and Applications

Abstract Single‐atom nanozymes (SAzymes) hold promise for cancer therapy but suffer from low active site density and restricted intermediate adsorption/desorption capabilities. Herein, Fe/Mo dual‐atom silicon‐based semiconductor nanozymes (FeMo DA ), encapsulated in lanthanide‐doped nanoparticles (LPs) and surface‐modified with hyaluronic acid (HA) (denoted as HA/FeMo DA ‐LPs), were developed for synergistic bienzymatic/upconversion‐triggered catalytic therapy (ET/UCT) under second near‐infrared (NIR‐II)/magnetic resonance (MR) imaging guidance. Density functional theory calculations revealed that Fe/Mo dual‐atom sites were bridged by Fe − O − Mo coordination, optimizing oxygen‐containing intermediate adsorption/desorption, and improving dual‐enzymatic activities. The peroxidase (POD)‐like catalytic performance of HA/FeMo DA ‐LPs showed a K m of 11.54 mM and a V max of 1.14 × 10 −7 M·s −1 , outperforming Fe‐ or Mo‐single‐atom coated LPs. HA modification promoted endocytosis (∼5.67‐fold) and microenvironmental acidification (pH from 7.21 to 6.74), further improving ET. Under 980 nm irradiation, upconversion‐triggered electrons synergized with oxidase‐like activity to convert O 2 into superoxide (•O 2 − ), while holes enabled •O 2 − to singlet oxygen ( 1 O 2 ) conversion, which combined with POD‐like‐produced hydroxyl radicals (•OH) to achieve synergistic ET/UCT. Tumor H + and glutathione co‐induced the specific degradation of nanozymes, resulting in tumor self‐enhanced downcon...