Dataset Information

Biomimetic engineering of a neuroinflammation-targeted MOF nanozyme scaffolded with photo-trigger released CO for the treatment of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is one of the most fatal and irreversible neurodegenerative diseases, which causes a huge emotional and financial burden on families and society. Despite the progress made with recent clinical use of inhibitors of acetylcholinesterase and amyloid-β (Aβ) antibodies, the curative effects of AD treatment remain unsatisfactory, which is probably due to the complexity of pathogenesis and the multiplicity of therapeutic targets. Thus, modulating complex pathological networks could be an alternative approach to treat AD. Here, a neutrophil membrane-coated MOF nanozyme (denoted as Neu-MOF/Fla) is biomimetically engineered to disturb the malignant Aβ deposition-inflammation cycle and ameliorate the pathological network for effective AD treatment. Neu-MOF/Fla could recognize the pathological inflammatory signals of AD, and deliver the photo-triggered anti-inflammatory CO and MOF based hydrolytic nanozymes to the lesion area of the brain in a spontaneous manner. Based on the in vitro and in vivo studies, Neu-MOF/Fla significantly suppresses neuroinflammation, mitigates the Aβ burden, beneficially modulates the pro-inflammatory microglial phenotypes and improves the cognitive defects of AD mice models. Our work presents a good example for developing biomimetic multifunctional nanotherapeutics against AD by means of amelioration of multiple symptoms and improvement of cognitive defects.

SUBMITTER: Liu C

PROVIDER: S-EPMC11339965 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Biomimetic engineering of a neuroinflammation-targeted MOF nanozyme scaffolded with photo-trigger released CO for the treatment of Alzheimer's disease.

Liu Chun C Zhang Wenting W Zhang Haochen H Zhao Chuanqi C Du Xiubo X Ren Jinsong J Qu Xiaogang X

Chemical science 20240718 33

Alzheimer's disease (AD) is one of the most fatal and irreversible neurodegenerative diseases, which causes a huge emotional and financial burden on families and society. Despite the progress made with recent clinical use of inhibitors of acetylcholinesterase and amyloid-β (Aβ) antibodies, the curative effects of AD treatment remain unsatisfactory, which is probably due to the complexity of pathogenesis and the multiplicity of therapeutic targets. Thus, modulating complex pathological networks c ...[more]

PMID: 39183930

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Project description:Antioxidant enzyme therapy shows promise for treating Alzheimer's disease (AD), but significant challenges remain in achieving effective blood-brain barrier (BBB) penetration and sustained therapeutic effects. We developed a novel neutrophil membrane (NM)-coated cerium-doped Prussian blue biomimetic nanozyme (NM@PB-Ce) that demonstrates outstanding enzymatic properties and targeted therapeutic efficacy. Extensive physicochemical characterization using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering confirmed the successful synthesis of uniform nanoparticles (~ 142 nm) with preserved membrane protein functionality. In vitro studies utilizing SH-SY5Y neuroblastoma cells revealed that NM@PB-Ce effectively scavenged reactive oxygen species through multiple enzyme-mimetic activities (catalase, superoxide dismutase, and peroxidase). The nanozyme significantly suppressed NLRP3 inflammasome activation and subsequent pyroptosis, reducing inflammatory markers (IL-1β, IL-18) while attenuating Aβ aggregation. Using a sophisticated co-culture BBB model and real-time in vivo fluorescence imaging, we demonstrated NM@PB-Ce's ability to traverse the BBB and accumulate specifically in AD-affected regions. In an Aβ1-42 oligomer-induced AD mouse model, systematic administration of NM@PB-Ce (320 μg/mL, 0.01 mL/g/day for 14 days) significantly improved cognitive performance across multiple behavioral paradigms, including the Morris water maze, Y-maze, and open field tests. Molecular and histological analyses revealed decreased neuroinflammation markers (GFAP, Iba-1) in the hippocampus, reduced levels of NLRP3, caspase-1, and phosphorylated tau (demonstrated by Western blot and ELISA), and enhanced dendritic spine density (visualized through Golgi staining). This comprehensive study establishes NM@PB-Ce as a promising therapeutic platform for AD treatment, providing both mechanistic insights into its mode of action and robust evidence of its therapeutic efficacy in targeting neuroinflammation and cognitive decline.

Project description:Rationale: Myocardial injury triggers intense oxidative stress, inflammatory response, and cytokine release, which are essential for myocardial repair and remodeling. Excess reactive oxygen species (ROS) scavenging and inflammation elimination have long been considered to reverse myocardial injuries. However, the efficacy of traditional treatments (antioxidant, anti-inflammatory drugs and natural enzymes) is still poor due to their intrinsic defects such as unfavorable pharmacokinetics and bioavailability, low biological stability, and potential side effects. Nanozyme represents a candidate to effectively modulate redox homeostasis for the treatment of ROS related inflammation diseases. Methods: We develop an integrated bimetallic nanozyme derived from metal-organic framework (MOF) to eliminate ROS and alleviate inflammation. The bimetallic nanozyme (Cu-TCPP-Mn) is synthesized by embedding manganese and copper into the porphyrin followed by sonication, which could mimic the cascade activities of superoxide dismutase (SOD) and catalase (CAT) to transform oxygen radicals to hydrogen peroxide, followed by the catalysis of hydrogen peroxide into oxygen and water. Enzyme kinetic analysis and oxygen-production velocities analysis were performed to evaluate the enzymatic activities of Cu-TCPP-Mn. We also established myocardial infarction (MI) and myocardial ischemia-reperfusion (I/R) injury animal models to verify the ROS scavenging and anti-inflammation effect of Cu-TCPP-Mn. Results: As demonstrated by kinetic analysis and oxygen-production velocities analysis, Cu-TCPP-Mn nanozyme possesses good performance in both SOD- and CAT-like activities to achieve synergistic ROS scavenging effect and provide protection for myocardial injury. In both MI and I/R injury animal models, this bimetallic nanozyme represents a promising and reliable technology to protect the heart tissue from oxidative stress and inflammation-induced injury, and enables the myocardial function to recover from otherwise severe damage. Conclusions: This research provides a facile and applicable method to develop a bimetallic MOF nanozyme, which represents a promising alternative to the treatment of myocardial injuries.

Dataset Information

Biomimetic engineering of a neuroinflammation-targeted MOF nanozyme scaffolded with photo-trigger released CO for the treatment of Alzheimer's disease.

Publications

Biomimetic engineering of a neuroinflammation-targeted MOF nanozyme scaffolded with photo-trigger released CO for the treatment of Alzheimer's disease.

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