Fe−O−Mo Site‐Activated Nanozymes for Bienzymatic/Upconversion Synergistic Catalytic Anticancer Therapy
Qiang Wang, Shuang Liu, Chunsheng Li, Yaru Huang, Boqi An, Meng Wang, Jiawei Qu, Peiyao Wang, Jiating Xu, Ping’an Ma
Abstract
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 downconversion NIR‐II and MR imaging. Compared with conventional SAzymes, HA/FeMo DA ‐LPs exhibit superior catalytic performance and dual‐modal imaging, offering a synergistic and tumor‐responsive platform for cancer theranostics.