Nanomaterials for Enzymatic Control of Oxidative Stress Toxicity and Free Radical Generation

Project Information

NESTOR

Grant agreement ID: 101007629

DOI

10.3030/101007629

Project closed

EC signature date 20 November 2020

Start date 1 October 2021

End date 31 March 2026

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 837 200,00

EU contribution

€ 837 200,00

Coordinated by

UNIVERSIDAD DE ZARAGOZA
Spain

Periodic Reporting for period 1 - NESTOR (Nanomaterials for Enzymatic Control of Oxidative Stress Toxicity and Free Radical Generation)

Reporting period: 2021-10-01 to 2024-03-31

Summary of the context and overall objectives of the project

Recent advances in nanotechnology have already provided excellent platforms to reshape many areas of biocatalysis and healthcare, and yet many challenges are still being faced to produce artificial nanozymes with better catalytic efficiency.
Pending achievements include having enhanced enzymatic robustness and stability while keeping the key aspects of natural enzymes such as high specificity, low toxicity and bioavailability. Consequently, there is currently a real demand for better designed nanozymes capable to solve these challenges for the different industrial and health requirements. NESTOR project aims to develop atomically-designed nanozymes based on versatile iron-oxide-based materials, to assess their true toxicological impact and to theoretically model the microscopic mechanisms of their enzymatic-like reactions (e.g. catalase-like, peroxidase-like, etc.) and to achieve a product-oriented enzymatic activity with minimum toxicological impact, a highly relevant societal concern. The outcomes from NESTOR project are expected to provide a better control of enzymatic reactions inside living entities together with the additional properties from the new materials such as magnetic actuability, imaging or heating. These research goals are embedded in the motivation of establishing a dynamic network with NESTOR, aimed to train the next generation of materials scientists, theoretical physicists, chemists, toxicologists and medical doctors in a highly interdisciplinary research environment so they can benchmark upcoming challenges concerning the new biomedical and environmental challenges to come. This next generation of open-minded scientists with true knowledge of multidisciplinary work will be an essential actor in the complex interactions between nanotechnologies and society that lay ahead.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the initial phase of the NESTOR project, the Consortium successfully accomplished most of the planned advancements in the manufacture and evaluation of Magnetic Nanozymes (MNZs), spanning from atomistic modeling to catalytic applications and in vitro toxicity testing. Within WP1 (Synthesis of Metal-Oxide Nanozymes and Atomistic Modelling), the Consortium produced initial batches of nanozymes, leading to the selection of the most efficient catalysts based on their performance. This portfolio includes various iron-oxide-based MNZs with MFe2O4 spinel ferrite structures, where M represents Fe, Mn, Cu, Zn, and V. Notable compositions include VxFe3-xO4, FeO, Fe3O4, MnxFe3-xO4, and CuxFe3-xO4, synthesized collaboratively by CSIC, CNEA, CONICET, and UNIZAR.

These MNZs were rigorously tested for their catalytic activity under WP2 (Structural and Physicochemical Characterization of Nanozymes), focusing on factors such as the role of surface metal ions, their oxidation states, local symmetry, and surface functionalization under various environmental conditions. The Consortium advanced a comprehensive assessment involving structural and magnetic characterization techniques, utilizing several HRTEM-based analytical tools like STEM-HAADF, EELS, and Dual Beam analysis, as well as magnetometry, XPS, PIXE, and Neutron Diffraction. Significant secondments and training efforts were made during the first period, enhancing the skill set of involved ESRs and ERs in these cutting-edge techniques at large facilities like Institut Laue Langevin in Grenoble, France, and ALBA accelerator in Barcelona, Spain.

Moving forward, the refined portfolio of nanozymes forms the cornerstone of ongoing exploration into their biomedical and catalytic applications, with potential adjustments based on emerging data on enzymatic performance. Additionally, within WP3 (Free Radicals and ROS Generation) and WP4 (Toxicological Characterization in vitro), the catalytic performance of these nanozymes was evaluated through their ability to produce Reactive Oxygen Species (ROS) via Fenton and Haber-Weiss reactions. The findings provided insights into the production of hydroxyl (•OH) and hydroperoxyl radicals (•OOH), and the influence of nanoparticle size, surface coating, and metal doping on these processes.

From a management perspective related to WP5 (Management, Dissemination, Communication), the NESTOR project encountered some delays initially due to complications arising from the COVID-19 pandemic. This unforeseen circumstance led to a change in the Grant Agreement, resulting in a delayed start date of October 1, 2021. While the pandemic's impact has lessened over time, it continued to affect the execution of certain planned secondments. Furthermore, the project faced an unforeseen partner withdrawal due to a force majeure health condition, impacting the execution of secondments mostly related to WP3 and WP4.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The NESTOR project has made several advancements beyond the current state of the art in the nanozyme biocatalysis area. The production and characterization of a diverse portfolio of iron-oxide-based MNZs with a comprehensive approach to synthesizing and rigorously testing these nanozymes for catalytic activity under various conditions represents a novel integration of methodologies and protocols. These MNZs have been catalogued based on our knowledge of the physicochemical properties, their catalytic mechanisms, and their genotoxicity in diffrerent cell models, constituing a portfolio for speficic, on demand uses.
This plattform allow to expect that the project is poised to deliver significant socio-economic and societal impacts. The development of efficient MNZs will impact the industrial sector in areas including environmental remediation, catalysis, and healthcare. The advancements in MNZ technology can lead to more effective and sustainable catalytic processes, reducing the environmental footprint of chemical manufacturing. In healthcare, the use of MNZs in diagnostics and treatment can enhance the effectiveness of therapies for conditions like cancer, offering more targeted and less invasive treatment options.

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