A Thrombin‐Activated Peptide‐Templated Nanozyme for Remedying Ischemic Stroke via Thrombolytic and Neuroprotective Actions

Abstract

Ischemic stroke (IS) is one of the most common causes of disability and death. Thrombolysis and neuroprotection are two current major therapeutic strategies to overcome ischemic and reperfusion damage. In this work, a novel peptide‐templated manganese dioxide nanozyme (PNzyme/MnO2) is designed that integrates the thrombolytic activity of functional peptides with the reactive oxygen species scavenging ability of nanozymes. Through self‐assembled polypeptides that contain multiple functional motifs, the novel peptide‐templated nanozyme is able to bind fibrin in the thrombus, cross the blood–brain barrier, and finally accumulate in the ischemic neuronal tissues, where the thrombolytic motif is “switched‐on” by the action of thrombin. In mice and rat IS models, the PNzyme/MnO2 prolongs the blood‐circulation time and exhibits strong thrombolytic action, and reduces the ischemic damages in brain tissues. Moreover, this peptide‐templated nanozyme also effectively inhibits the activation of astrocytes and the secretion of proinflammatory cytokines. These data indicate that the rationally designed PNzyme/MnO2 nanozyme exerts both thrombolytic and neuroprotective actions. Giving its long half‐life in the blood and ability to target brain thrombi, the biocompatible nanozyme may serve as a novel therapeutic agent to improve the efficacy and prevent secondary thrombosis during the treatment of IS.

Recent Advancements in the Formulation of Nanomaterials-Based Nanozymes, Their Catalytic Activity, and Biomedical Applications

“…It also alleviates production of pro-inflammatory cytokines by inhibiting astrocytes activation as well. 80 The bioinspired Cdot nanozyme is endowed with high superoxide dismutase enzymatic activity and displays red fluorescence through surface modification of its functional group that accelerates the disproportionation reaction of formed superoxide radicals. These structural advances effectively endocytose the nanozyme thus alleviating ROS levels and pro-inflammatory factors and therefore provide a greater possible way to treat ROS-related illness and imaging of biological processes in vivo.…”

The rational design of nanozymes for imaging-monitored cancer therapy

“…Mn affects the metabolism and redox steady state in tumor cells due to its multiple valences and high spin. 69,70 Many scientists have studied Mn-based nanozymes in the wake of natural selection, and diverse Mn-based nanomaterials have shown a range of enzyme-like functions, including glutathione peroxidase, 3,71–74 catalase, 73,75–80 superoxide dismutase, 80,81 and peroxidase. 82,83…”

“…Mn affects the metabolism and redox steady state in tumor cells due to its multiple valences and high spin. 69,70 Many scientists have studied Mn-based nanozymes in the wake of natural selection, and diverse Mn-based nanomaterials have shown a range of enzyme-like functions, including glutathione peroxidase, 3,[71][72][73][74] catalase, 73,[75][76][77][78][79][80] superoxide dismutase, 80,81 and peroxidase. 82,83 A versatile mesoporous nanozyme was created by Wang and colleagues from MnCo-MOFs to increase the effectiveness of PDT under the guidance of bioimaging 77 (Fig.…”

Development of nanozyme based sensors as diagnostic tools in clinic applications: a review

“…The most researched and widely utilized NZs for biological sensing, molecular detection, immunoassays, and theragnostic applications are those that have activities similar to those of oxidase (OD), peroxidase (POD), catalase (CAT), and superoxidase dismutase (SOD). 22–25…”

“…The most researched and widely utilized NZs for biological sensing, molecular detection, immunoassays, and theragnostic applications are those that have activities similar to those of oxidase (OD), peroxidase (POD), catalase (CAT), and superoxidase dismutase (SOD). [22][23][24][25] Nanozymes are nanomaterials that catalyze efficient biochemical reactions such as oxidation, reduction and hydrolysis. They can imitate enzyme active areas and perform similar tasks as natural enzymes.…”