Hybrid nanozymes for biomedical applications
Host organizations
Hiring Institution
École Centrale de Lyon (EC Lyon)
PhD-Awarding Institutions
École Centrale de Lyon (EC Lyon)
RMIT University (RMIT)
Position Description
Proposed projects
Note: This project will involve the use of chemicals, which will be handled according to the safety data sheets provided by the supplier. The institutions will provide training and protection equipment.
Option 1
Hybrid nanozymes with synergetic catalytic activity as antimicrobial agents
Nanozymes are nanoparticles with catalytic properties that can mimic the behaviour of natural enzymes [Walther 2018]. Reactive oxygen species (ROS) can be generated by different nanozymes. These ROS can be used for photodynamic therapy as they can trigger the death of pathogens such as bacteria or cancer cells [Maddheshiya 2022]. The reactive surface of metal nanoparticles associated to their large specific surface area make them interesting candidates for these therapeutic applications [Liu 2021]. In addition, iron oxide nanoparticles can be also considered as nanozymes [Gao 2007], as well as hyperthermic agent. Furthermore, they can be actuated with an external magnetic field.
The objectives of the thesis will be to design new nanoparticles composed of an iron oxide core and a metal seeds shell and to use them for the capture and elimination of bacteria from complex media. We recently demonstrated that the resulting vicinity of the two nanomaterials (noble metal seeds/oxide nanoparticles) in the nanozymes give rise to new catalytic activities or synergies by mimicking the colocalization of enzymatic activities as cells do. To capture bacteria and amplify the antimicrobial effect, peptides such as magainin, will be immobilized onto nanoparticles surface.
The PhD student will work in a first step on the chemical modification of iron oxide nanoparticles surfaces to graft noble metal nanocatalyzers. The structural and surface properties of nanoparticles will be characterized at INL by Transmission Electron Microscopy (TEM), zetammetry, infrared spectroscopy and photoelectron spectroscopy. Then, the catalytic activity of nanozymes will be evaluated through the oxidation of a coloured substrate (TMB) or a fluorescent substrate.
Finally, the candidate will study the antimicrobial activity of nanozymes at RMIT Melbourne. Two non-academic partners based in France will be involved in this project. The first is Beaujon Hospital (AP-HP, Paris) and in particular the Endoscopy service. Indeed, one application that will be investigated in this project will be the design of antibacterial surfaces for endoscopes using nanozymes. The second is SON SAS, a company specialized in the conception and production of metal-modified iron oxide nanoparticles.
Option 2
Hybrid nanozyme biosensors with synergetic catalytic activity for the detection of agricultural analytes
The sensitive on-field detection of deleterious biological or chemical entities for the management of crop is of key importance for the preservation of the environment. Therefore, we aimed at the development of a colorimetric assays based on the catalytic activity of multimaterial nanoparticles for the detection of entities involved in crop protection. Indeed, many colorimetric biossays (for example ELISA) are based on the oxidation of a dye mediated by an enzyme leading to a change of colour. Herein, we aimed at replacing the catalytic activity of natural enzymes by the so-called nanozymes. Nanozymes are nanoparticles with catalytic properties that can mimic the behaviour of natural enzymes [Walther 2018]. Herein, the combination of, metal nanocatalyzers on oxide nanoparticles will allow increasing their oxidative activity, because oxidation reactions are preferentially achieved onto oxygen vacancies [Song 2013 & Qin 2019].
The specificity of the assay can be addressed using aptamers which can interact selectively with given entities. Indeed, the presence of aptamers onto nanoparticles surface blocks the catalytic properties of the nanozyme. When the biological targets interact with the aptamers, the aptamers leave the surface and the oxidation activity is restored. Using the specificity of aptamers, any kind of biological target (oligonucleotides, proteins, cells, bacteria) could be detected. For example, it was recently shown that nanozymes can be used as ultrasensitive and ultrafast biosensors able to detect target molecules with a concentration as low as 0.1 ppm and in few minutes, using aptamers as bioreceptors [Sharma 2014].
The objectives of the thesis will be to design new nanoparticles composed of an oxide core with nanometric noble metal seeds deposited on its surface and to use them as nanozymes for the detection of several targets of agricultural and environmental importance, such as pesticides, per- and poly-fluoroalkyl substances (PFAS) and plant viruses.
The PhD student will work in a first step on the chemical modification of oxide nanoparticles surfaces to graft noble metal nanocatalyzers. To achieve this, he(she) will use different polyelectrolytes to monitor metal seeds surface density. In a second step, he(she) will select specific aptamers and adsorb them onto hybrid nanoparticles surface. At each step, the structural and surface properties of nanoparticles will be characterized at INL by Transmission Electron Microscopy (TEM), zetammetry, infrared spectroscopy and photoelectron spectroscopy. Then, the catalytic activity of nanozymes will be evaluated through the oxidation of colour- or fluorescence-generating substrates. Finally, the candidate will perform the detection of several agricultural analytes at RMIT Melbourne and will evaluate biosensor performances (detection threshold, sensitivity, selectivity) depending on the hybrid nanoparticles structural and surface properties. Two non-academic partners based in Melbourne, Universal Biosensors, a nanosensor manufacturing company, and DAFF, the Australian Government’s Department of Agriculture, Fisheries and Forestry will be integrally involved as the potential end-users to facilitate technology adoption towards the end of the project.
Option 3
Anti-oxidative properties of nanohybrids
The generation of reactive oxygen species (ROS) and more generally of free radicals, is at the origin of many health issues such as liver diseases (hepatitis for instance) or cancers. They can also be produced as a consequence of poisoning by environmental pollutants (heavy metals, acid, base, halogen,…) or radiations (such as X-Ray used in radiation therapy). The resulting oxidative stress can cause damage or even apoptosis of cells.
It was shown that nanoparticles can eliminate the excess of cellular ROS and be used as free radicals scavengers [Huang 2016].
The objectives of the thesis will be to design new nanoparticles composed of an oxide core and a metal seeds shell and to test their anti-oxidative properties onto bacteria and cancer cells. Indeed, we recently demonstrated that the resulting vicinity of the two nanomaterials (noble metal seeds/oxide nanoparticles) in the nanozymes give rise to new catalytic activities or synergies by mimicking the colocalization of enzymatic activities as cells do.
The PhD student will work in a first step on the chemical modification of oxide nanoparticles surfaces to graft noble metal nanocatalyzers. The structural and surface properties of nanoparticles will be characterized at INL by Transmission Electron Microscopy (TEM), zetammetry, infrared spectroscopy and photoelectron spectroscopy. Then, the catalytic activity of nanozymes will be evaluated through the oxidation of a coloured substrate, TMB. Finally, the candidate will study the anti-oxidative activity of nanozymes at RMIT Melbourne. A non-academic partner based in Melbourne, DAFF, the Australian Government’s Department of Agriculture, Fisheries and Forestry will be integrally involved as a potential end-user to facilitate technology adoption towards the end of the project.
Supervisors
Research Areas
Chemistry, Biochemistry, Nanotechnologies