Single‐Atom Nanozyme with Asymmetric Electron Distribution for Tumor Catalytic Therapy by Disrupting Tumor Redox and Energy Metabolism Homeostasis

Abstract

Nanozyme catalytic therapy triggered by tumor‐specific endogenous stimuli is an emerging tumor therapy that attracts wide attention. However, the current therapeutic efficacy of nanozyme catalytic therapy is severely limited by the catalytic efficiency of nanozymes and the concentration of endogenous reaction substrates. Herein, a novel and efficient IrN5 single‐atom (IrN5 SA) nanozyme is developed with multiple enzyme‐like catalytic activities. Due to the synergistic effect of central Ir single‐atom and axial N coordination, IrN5 SA exhibits better enzymatic catalytic performance than IrN4 SA. At tumor sites, IrN5 SA can generate a large amount of reactive oxygen species (ROS) through oxidase (OXD)‐like and peroxidase (POD)‐like catalytic activities. Moreover, IrN5 SA can also generate O2 and hydrogen peroxide (H2O2) through catalase (CAT)‐like and nicotinamide adenine dinucleotide (NADH) oxidase (NOX)‐like catalytic activities, realizing the efficient nanozyme catalytic therapy in a substrate‐cycle manner. Additionally, IrN5 SA can effectively break the intracellular NADH/NAD+ cycle balance by mimicking NOX, and then cooperate with fatty acid synthase cerulenin (Cer) to interfere with the energy metabolism homeostasis of tumor cells. Consequently, the designed IrN5 SA/Cer nanoagent can disrupt redox and metabolic homeostasis in the tumor region through an enzyme‐mimicking cascade reaction, effectively overcoming the shortcomings of current nanozyme catalytic therapy.

Boosting Ferroptosis Therapy with Iridium Single‐Atom Nanocatalyst in Ultralow Metal Content

“…[11] Recently, Ir(III) complexes have attracted great attention in biomedical research due to their potential chemotherapeutic properties; [12] however, the biomedical implications of Ir-based nanocatalysts has rarely been reported and need to be explored in depth. [13] We proposed that the coordination and charge transfer potentials would be beneficial for Ir atoms in catalytic therapy, as those explored in nanozymes. [14] Here, we prepared iridium single atoms on a nitrogendoped carbon composite (Ir 1 /CN SAC) with an ultralow metal content and fully exposed active sites.…”

Copper Single-Atom Jellyfish-like Nanomotors for Enhanced Tumor Penetration and Nanocatalytic Therapy

“…The optimum catalytic condition is around pH 5.0–6.0, which is beneficial to trigger specific therapy in the weak acid environment of tumors. The steady-state kinetics of Cu-JMCNs can be obtained by calculating the oxidation velocity of TMB (Figure S12), − giving k m = 0.37 mM and v max = 4.6 × 10 –7 M/s for H 2 O 2 .…”

Nanozymes Based on MXene Nanosheets Decorated with Pt Nanoparticles for Hyperthermal-Enhanced Cascade Catalytic Therapy of Tumors

“…Realizing efficient and less toxic treatments for cancer is always the focus of research . Together with the development of nanomedicine, nanocatalytic therapy provides new perspectives for the treatment of cancer. , Catalytic therapy mainly involves a chemical reaction in situ within the tumor with catalytically active nanomaterials to produce toxic substances to kill tumor cells. , Nanozymes are attracting widespread attention in the field of catalytic medicine since they contain the catalytic activity of natural enzymes and the physicochemical properties of nanomaterials. − In recent years, multiple nanozymes are emerging, including carbon-based nanozymes, iron-based nanozymes, manganese-based nanozymes, , and single-atom nanozymes, − which are widely used for detection, disease therapy, and especially nanozyme-mediated tumor catalytic therapy. − …”