Edge‐Site Engineering of Defective Fe–N₄ Nanozymes with Boosted Catalase‐Like Performance for Retinal Vasculopathies

Abstract

Extensive efforts are devoted to refining metal sites for optimizing the catalytic performance of single‐atom nanozymes (SANzymes), while the contribution of the defect environment of neighboring metal sites lacks attention. Herein, an iron‐based SANzyme (Fe‐SANzyme) is rationally designed by edge‐site engineering, which intensively exposes edge‐hosted defective Fe–N4 atomic sites anchored in hierarchical mesoporous structures. The Fe‐SANzyme exhibits excellent catalase‐like activity capable of efficiently catalyzing the decomposition of H2O2 into O2 and H2O, with a catalytic kinetic KM value superior to that of natural catalase and reported nanozymes. The mechanistic studies depict that the defects introduce notable charge transfer from the Fe atom to the carbon matrix, making the central Fe more activated to strengthen the interaction with H2O2 and weaken the OO bond. By performing catalase‐like catalysis, the Fe‐SANzyme significantly scavenges reactive oxygen species (ROS) and alleviates oxidative stress, thus eliminating the pathological angiogenesis in animal models of retinal vasculopathies without affecting the repair of normal vessels. This work provides a new way to refine SANzymes by engineering the defect environment and geometric structure around metal sites, and demonstrates the potential therapeutic effects of the nanozyme on retinal vasculopathies.

Engineering Single-Atom Iron Nanozymes with Radiation-Enhanced Self-Cascade Catalysis and Self-Supplied H2O2 for Radio-enzymatic Therapy

“…Chemically engineering nanomaterials to exert potent anticancer activity, such as radiosensitizing cancer cells, − exhausting energy metabolism, − and generating reactive oxygen species (ROS), − has the promising potential to achieve satisfactory therapeutic outcomes. More recently, inspired by natural metalloenzymes, − fine-defined single-atom nanozymes (SAzymes), in which metal atoms as active sites are monodispersed on supports, have drawn significant attention for their ability to trigger abnormally low or high levels of intracellular biomarkers through catalysis to induce cancer-specific cytotoxicity, thereby rapidly emerging as a competitive alternative for therapeutic use in oncology. − For instance, oxidoreductase-like SAzymes that respond to the tumor microenvironment enable the conversion of less reactive H 2 O 2 into highly cytotoxic hydroxyl radicals ( • OH) for chemodynamic therapy or into O 2 for overcoming tumor hypoxia toward the following treatments. − However, the catalytic active sites of most SAzymes are identified predominantly as their superficial atoms rather than their inner moieties, which severely limits therapeutic efficacy as the result of this deficient catalytic activity. − Moreover, intratumoral H 2 O 2 , although it is higher compared to normal cells, remains largely insufficient, thus presenting another challenge to enzymatic therapy owing to H 2 O 2 -dependent • OH generation. − In addition, overexpressed glutathione (GSH) can quickly consume • OH produced by SAzymes at the tumor sites, further blunting its anticancer efficacy. − …”

Breakthroughs in nanozyme-inspired application diversity

“…Based on the H & E staining result, Fe-SANzyme was suggested as a secure and efficient antioxidant medication of ocular retinopathy. 89…”

“…Based on the H & E staining result, Fe-SANzyme was suggested as a secure and efficient antioxidant medication of ocular retinopathy. 89 As the systemic inflammatory response syndrome, sepsis is one of the oxidation-related inflammatory diseases brought on by microbial infections. Yang et al designed Cu-SAzyme, which demonstrated excellent SOD-mimic properties for O 2 À elimination as well as desirable stability over a broad range of pH and temperature.…”

Self-Adapting Graphitic C6N6-Based Copper Single-Atom Catalyst for Smart Biosensors

“…Interestingly, these oxidation reactions are catalyzed by carbon nitrides via different reactive oxygen-related intermediates under similar conditions, except for light irradiation. [45][46][47][48][49] As such, we reason that the multiformity of carbon nitrides in oxidation processes would offer an intriguing way to solve the inconsistency of reaction conditions in realizing the basic activity and the gain effect for self-adaptability; however, to our knowledge, this has rarely been reported.…”