Bioinspired porous three-coordinated single-atom Fe nanozyme with oxidase-like activity for tumor visual identification via glutathione

Inspired by structures of natural metalloenzymes, a biomimetic synthetic strategy is developed for scalable synthesis of porous Fe-N(3) single atom nanozymes (pFeSAN) using hemoglobin as Fe-source and template. pFeSAN delivers 3.3- and 8791-fold higher oxidase-like activity than Fe-N(4) and Fe(3)O(4) nanozymes. The high catalytic performance is attributed to (1) the suppressed aggregation of atomically dispersed Fe; (2) facilitated mass transfer and maximized exposure of active sites for the created mesopores by thermal removal of hemoglobin (2 ~ 3 nm); and (3) unique electronic configuration of Fe-N(3) for the oxygen-to-water oxidation pathway (analogy with natural cytochrome c oxidase). The pFeSAN is successfully demonstrated for the rapid colorimetric detection of glutathione with a low limit of detection (2.4 nM) and wide range (50 nM–1 mM), and further developed as a real-time, facile, rapid (~6 min) and precise visualization analysis methodology of tumors via glutathione level, showing its potentials for diagnostic and clinic applications.