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

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(9)

Published: Nov. 14, 2022

Nanozyme catalytic therapy triggered by tumor-specific endogenous stimuli is an emerging tumor that attracts wide attention. However, the current therapeutic efficacy of nanozyme severely limited efficiency nanozymes and concentration reaction substrates. Herein, a novel efficient IrN5 single-atom (IrN5 SA) developed with multiple enzyme-like activities. Due to synergistic effect central Ir axial N coordination, SA exhibits better enzymatic performance than IrN4 SA. At sites, can generate large amount reactive oxygen species (ROS) through oxidase (OXD)-like peroxidase (POD)-like Moreover, also O2 hydrogen peroxide (H2 ) catalase (CAT)-like nicotinamide adenine dinucleotide (NADH) (NOX)-like activities, realizing in substrate-cycle manner. Additionally, effectively break intracellular NADH/NAD+ cycle balance mimicking NOX, then cooperate fatty acid synthase cerulenin (Cer) interfere energy metabolism homeostasis cells. Consequently, designed SA/Cer nanoagent disrupt redox metabolic region enzyme-mimicking cascade reaction, overcoming shortcomings therapy.

Language: Английский

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Oxygen Self‐Supply Engineering‐Ferritin for the Relief of Hypoxia in Tumors and the Enhancement of Photodynamic Therapy Efficacy

Small, Journal Year: 2022, Volume and Issue: 18(15)

Published: Feb. 25, 2022

Hypoxia is a hallmark of the tumor microenvironment (TME) that promotes development and metastasis. Photodynamic therapy (PDT) promising strategy in treatment tumors, but it limited by lack oxygen TME. In this work, an O2 self-supply PDT system constructed co-encapsulation chlorin e6 (Ce6) MnO2 core engineered ferritin (Ftn), generating nanozyme promoted nanoformula (Ce6/Ftn@MnO2 ) for therapy. Ce6/Ftn@MnO2 exhibits uniform small size (15.5 nm) high stability due to inherent structure Ftn. The fluorescence imaging immunofluorescence analysis demonstrate pronounced accumulation tumors mice, significantly decreases expression hypoxia-inducible factor (HIF)-1α. nanoplatform exerts more potent anti-tumor efficacy with negligible damage normal tissues compared free Ce6. Moreover, weak acidity presence H2 TME enhances r1 relativity , resulting prominent enhancement MRI tumor. This bio-mimic Ftn not only improves vivo distribution retention Ce6, also effectiveness precision modulation.

Language: Английский

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Reaction Mechanisms and Kinetics of Nanozymes: Insights from Theory and Computation

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(10)

Published: Jan. 15, 2023

Abstract “Nanozymes” usually refers to inorganic nanomaterials with enzyme‐like catalytic activities. The research into nanozymes is one of the hot topics on horizon interdisciplinary science involving materials, chemistry, and biology. Although great progress has been made in design, synthesis, characterization, application nanozymes, study underlying microscopic mechanisms kinetics still not straightforward. Density functional theory (DFT) calculations compute potential energy surfaces along reaction coordinates for chemical reactions, which can give atomistic‐level insights micro‐mechanisms nanozymes. Therefore, DFT have playing an increasingly important role exploring past years. either predict details processes complement experiments or further develop theoretical models depict physicochemical rules. In this review, corresponding summarized. Particularly, review focuses computational studies that closely interplay experiments. relevant experimental results without will be also briefly discussed offer a historic overview how computations promote understanding

Language: Английский

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Tumor Microenvironment-Activable Manganese-Boosted Catalytic Immunotherapy Combined with PD-1 Checkpoint Blockade

ACS Nano, Journal Year: 2022, Volume and Issue: 16(12), P. 20400 - 20418

Published: Nov. 28, 2022

Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state tumor microenvironment (TME), therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB kill tumors efficiently. The cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnOx) nanozyme termed CM@Mn showed intrinsic peroxidase oxidase-like activities an acidic TME. These can generate toxic hydroxyl (•OH) superoxide radicals (•O2-) killing evoking immunogenic death (ICD). Furthermore, TME-responsive release of Mn2+ directly promotes dendritic maturation macrophage M1 repolarization, resulting reversal immunosuppressive TME into immune-activating environment. Additionally, hypoxia relief caused by catalase-like activity also contributes process reversal. Finally, robust tumor-specific T cell-mediated antitumor response occurs support PD-1 blockade. proliferation primary metastatic was inhibited, long-term memory effect induced. strategy outlined here may serve as promising candidate tumor-integrated

Language: Английский

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“Three‐in‐One” Nanozyme Composite for Augmented Cascade Catalytic Tumor Therapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 18, 2023

Abstract Cascade catalytic reaction exhibits simple procedure and high efficiency, such as that from the orderly assembly of different enzymes in biological systems. Mimicking natural cascade becomes critical, but is still challenging. Herein, single Au–Pt nanozyme reported with “three‐in‐one” functions to initiate conversions for O 2 supply mimic catalase, H production its glucose oxidase‐like property, • OH generation peroxidase chemodynamic therapy (CDT). Thus, complex cross‐talk among are avoided. To this end, metastable Cu NPs, scaffolds, used anchor ultrasmall nanozyme, while metal–organic framework (MOF) encapsulate tumor microenvironment response shielding protein adsorption. Pluronic F127 then modified on surface improve hydrophilicity biocompatibility composite. The endogenous acidity glutathione degrade MOF expose CDT. photothermal conversion ability also enhances CDT, 2+ ions consume GSH further CDT efficiency augmented therapy. a new paradigm provided drug‐free improving therapeutic efficacy minimizing side effects.

Language: Английский

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