Computational Design and Engineering of Metal Oxide Nanozymes

Lead Research Organisation: University of Huddersfield
Department Name: Chemical Sciences

Abstract

The average age of UK population is increasing and a rise in diseases related to accumulation of radical species in living cells, i.e. oxidative stress, is reported. To achieve a "Healthy Nation", there is therefore a need to develop cost-effective and high efficient nanotechnologies for prevention, diagnosis and therapy of diseases that are caused or can cause oxidative stress. Oxidative stress has been linked to degenerative diseases and cancer. Radicals are normally regulated by enzymes but when they accumulate, we need a technology that can control their concentration. Nanozymes can mimic enzyme activities and regulate the concentration of radicals in living cells. Thus, the importance of understanding and developing materials for nanozymes based technologies.

This computational project will use a combination of different modelling techniques to develop nanotechnologies based on metal oxide nanoparticles that are able to mimic enzyme activity towards the scavenging of radicals. As the enzyme-mimetic activities depends on the surface composition and reactivity of the metal oxide nanoparticles, it is important to gain insights at the nanoscale. Therefore, computational techniques based on both ab initio and classical methods will be used to gain information that is complementary to experimental findings.

This project is multidisciplinary as it brings together materials science and biomedicine through a research team of computational and experimental researchers. Advanced functional materials with enzyme-mimetic activity can regulate radicals in biological environments. These nanozymes, however not always present a simple enzyme-mimetic activity but rather they show a complex behaviour. This is due to their high reactivity at their surface.

We will focus our attention on nanoceria, a material that showed value as a protective agent for cellular aging, neurodegenerative disorders, cardiovascular pathologies, retinal degeneration, cancer treatment and tissue engineering. Nanoceria displays high surface reactivity and can mimic enzymes such as superoxide dismutase and catalase that regulate superoxide radicals and hydrogen peroxide, respectively. However, the exploitation of these two functions is altered by other surface activities such as the phosphatase activity and the adsorption of phosphates on nanoceria surfaces. Whereas experimental work is hindered by the complexity of the biological environments, computational work can attain information at the atom level and provide insights into the surface processes and reactivity. Therefore, this project will evaluate the surface composition and reactivity of nanoceria in the presence of biologically relevant oxyanions such as phosphates and identify the factors controlling nanoceria radical scavenging activity. We will then use these to generate guidelines to design and engineer nanoceria morphologies with enhanced enzyme-mimetic activities towards the scavenging of radicals. This will ultimately benefit the development of healthcare nanotechnologies based on the use of nanozymes.

Planned Impact

This project is in line with the prosperity outcomes of the UK development plan 2016/17-2019/20 for the Healthy Nation ambitions "Optimisation of diagnosis and treatment", "Development of future therapeutic technologies", and "Transformation of community healthcare". These are also translated in the EPSRC Healthcare Technologies Grand Challenges.

The average age of UK population is increasing and a rise in diseases related to accumulation of radical species, i.e. oxidative stress, is reported. There is therefore a need for developing low cost and high efficient nanotechnologies for prevention, diagnosis and therapy of diseases that are caused or can cause oxidative stress. Nanozymes can mimic enzymes and regulate the concentration of radicals in living cells. The development of nanozymes based technologies will require the development of biocompatible advance functional materials and a full understanding of their surface catalytic properties. This can be translate into efficient sensing systems that can be implemented in cost-effective and reliable medical devices. Nanozymes can be implemented in immunoassays, logical monitoring gates, point-of-care testing (POCT) for diagnosis at the time and place of patient care rather than awaiting for medical laboratory analysis, as well as in future therapeutic technologies. Of course, their implementation in clinical practice will have to conform to the UK regulation and pass relevant clinical trials. Whereas this project will not deliver a functioning medical device, it will provide a computational procedure to determine and assess the enzyme mimetic activities of metal oxide nanoparticle as nanozymes. This procedure will be then developed in a large grant submission to EPSRC. As computational techniques are cheaper than in vitro and in vivo experimentation, the development of computational methodologies that can be routinely used will be cost-effective in the long term and if fully developed it will help avoiding the use of animals and human in clinical trials, which are always cause of growing ethical concern.

The results stemming from this project will make a key contribution to the UK's research leadership in materials for biomedical applications and to a broader extend to catalysis applications. The UK has a large investment in nanomaterials, with currently over 20 Micro and Nano Technologies (MNT) Centres, and the number of companies active in biological nanomaterials are second only to those active in the thin films and nanocoating. Involvement with the commercial and private sector will be embedded at several levels. Firstly, the University of Huddersfield Research and Enterprise team will provide support in the identification of intellectual properties and opportunities for commercial exploitation of research. Help will also be provided by Dr Seal who has extensive experience in patenting (over 60 patents). More feasible patents may include those on the design of nanozymes with enhanced enzyme mimetic activities. Secondly, the University of Huddersfield Business Development Team will support the development of industrial partnerships needed to the identification of opportunities to take the results further via further RCUK funding and applications in partnership with healthcare technologies companies via Innovate UK, e.g. via the KTP scheme were the University of Huddersfield has an excellent track record. This will bear the ultimate translation of research findings into real applications. To facilitate contact with the commercial sector, a workshop will also be held after the first 6 months of the project.

Publications

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Andrews R (2020) Self-Assembled Anion-Binding Cryptand for the Selective Liquid-Liquid Extraction of Phosphate Anions. in Angewandte Chemie (International ed. in English)

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Castanet U (2019) Controlling the {111}/{110} Surface Ratio of Cuboidal Ceria Nanoparticles. in ACS applied materials & interfaces

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Jackson FF (2019) Droplet Misalignment Limit for Inkjet Printing into Cavities on Textured Surfaces. in Langmuir : the ACS journal of surfaces and colloids

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Morgan LM (2018) Protecting Ceria Nanocatalysts-The Role of Sacrificial Barriers. in ACS applied materials & interfaces

 
Description Nanozymes are nanoparticles with enzyme mimetic activity and they can be used in diagnosis and treatment of cancer and degenerative diseases. We need to develop ways to control the relationship between their structure and their properties. As nanoceria, a promising nanozyme enters the living cell, we need to be able to control its surface properties. We have started mapping the effect of an important bodily electrolyte on the surface chemistry of nanoceria. On the other hand the exploitation of materials surface properties is dependent on their nanostructure which included intrinsic and extrinsic point defects, and extended defects such as surfaces, dislocations and grain-boundaries. The research undertaken so far is related to morphological and compositional effects of nanoceria and related fluorite structures, to provide a variety of models that can be used for future studies.
Exploitation Route A consistent computational procedure to evaluate the surface chemistry of nanozymes can be used to screen across many materials. This could be implemented in a large scale dataset of surfaces and interfaces like the UK based "Surface and Interface Toolkit for the Materials Chemistry Community".
Sectors Energy,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The impact is to the experimental project partner (University of Central Florida) about the interaction of nanoceria with a bodily electrolyte (phosphate). This allows for a better understanding of the reactivity and usefulness of ceria as a crystalline nanomedicine. Nanoparticles with enzyme mimetic activity are nanozymes and their exploitation in biomedicine is extremely promising in research on aging, cancer and degenerative diseases.
Sector Energy,Pharmaceuticals and Medical Biotechnology
 
Title Cuboidal Ceria Nanoparticles 
Description Data needed to reproduce Controlling the {111}/{110} surface Ratio of Cuboidal Ceria Nanoparticles 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact dataset related to Controlling the {111}/{110} surface Ratio of Cuboidal Ceria Nanoparticles 
URL https://huddersfield.box.com/s/hwgks9sl2gngdqap4nv348blxuv5ifac
 
Title Nanoceria Structures as Enzyme Mimetic Agents 
Description This is in support of Computer-Aided Design of Nanoceria Structures as Enzyme Mimetic Agents: The Role of Bodily Electrolytes on Maximising Their Activity. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact This is in support of Computer-Aided Design of Nanoceria Structures as Enzyme Mimetic Agents: The Role of Bodily Electrolytes on Maximising Their Activity. 
URL https://huddersfield.box.com/s/lyvzmh0q2xnhfgm5cytxnum43gf7mtr6
 
Title intermediate oxygen clusters 
Description data related to The impact of Hydrogen on the intermediate oxygen clusters and diffusion in Fluorite Structured UO2+x 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact data related to The impact of Hydrogen on the intermediate oxygen clusters and diffusion in Fluorite Structured UO2+x 
URL https://huddersfield.box.com/s/090jx75fvntzvy9ksuy0b45uys2uaqpm
 
Description Dean C. Sayle 
Organisation University of Kent
Department School of Physical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Data sharing: reactivity of nanoceria. Staff time: project direction, methods for generating atom-level models. Skills transfer between groups: model generation and electronic structure simulations. Mapping future grant directions.
Collaborator Contribution Data sharing: library of atom-level models of nanomaterials - catalytically active models of nanoceria. Staff time: project direction, methods for generating atom-level models. Skills transfer between groups: model generation and electronic structure simulations. Mapping future grant directions.
Impact Research outputs are listed in https://orcid.org/0000-0001-7144-6075. Dr. Dean C. Sayle is also a project partner on EP/R010366/1. This collaborations involve multiscale modelling using different computational approaches at different level of theory.
Start Year 2012
 
Description Sudipta Seal 
Organisation University of Central Florida
Country United States 
Sector Academic/University 
PI Contribution Informative discussion to guide the development of research. Data sharing, specifically sharing the experimental observation of nanoceria catalytic activity as function of pH, and constituents of different media. Opportunities for improving experiments by accounting for enhanced design.
Collaborator Contribution Informative discussion to guide the development of research. Data sharing, specifically sharing the experimental observation of nanoceria catalytic activity as function of pH, and constituents of different media. Opportunities for improving simulations by accounting for experimental complexity.
Impact Research outputs on https://orcid.org/0000-0001-7144-6075. Prof. Sudipta Seal is a project partner on EP/R010366/1. Our collaboration links the experimental observation and modelling prediction of materials relevant for energy and biomedical applications.
Start Year 2013