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Surface functionalized nanodiamonds for antimicrobial applications

Primary Supervisor: Professor Haitao Ye, School of Engineering

Secondary Supervisor: Professor Marco R. Oggioni, Department of Microbial Genetics

PhD project title:: Surface functionalized nanodiamonds for antimicrobial applications

University of Registration: University of Leicester

Project outline: 

Objective: The project is to develop novel surface functionalized nanodiamonds for antimicrobial applications against antibiotic resistant bacteria.

Background: Antimicrobial resistance (AMR) has been identified as one of the main challenges facing the 21st century, and presents a spectrum of complex and multifaceted questions, ranging in scope from fundamental scientific research at the horizons of disciplines through to the behaviour of individuals and society. The need for novel antibiotics comes from the high incidence of bacterial infection and the growing resistance of bacteria to conventional antibiotics; new methods for reducing bacterial activity and associated infections are badly needed. Nanotechnology, the use of materials with dimensions on the atomic or molecular scale, has become increasingly utilized for medical application and is of great interest as an approach to killing or reducing the activity of numerous microorganisms. Several classes of antimicrobial nanomaterials (such as Ag, Cu, ZnO, Fe3O4, Al2O3, TiO2, SiO2) and nanosized carriers for antibiotic delivery have shown some effectiveness for treating infectious diseases, including those caused by antibiotic-resistant organisms, in vitro and in animal models. In order to be practical in clinical application, these nanomaterials need to fulfil several requirements: broad availability, easy and stable surface functionalization, dispersibility in aqueous solution, non-toxicity and environmental friendliness. Among the many promising nanomaterials, nanodiamond particles (NDs) are receiving increased attention as they comply with all of these prerequisites. NDs demonstrated an innate compatibility with biological environments and low toxicity in comparison with other nanoscale structures. The readily modifiable surface, which is easily functionalised, has enabled NDs to be conjugated to specific molecules, opening a plethora of biomedical applications that include orthopaedic engineering, synthesis of contact lenses , single cell magnetometry, toxicity studies in worms and rodents, cancer stem cell targeting, targeted breast cancer therapy and pharmaceutical delivery. Moreover, NDs can be made hydrophilic or hydrophobic, are available in large quantities, and are proven safe and biocompatible. ND possesses several other advantages over other nanoparticles and objects (like carbon nanotubes or polymer NP), such as not swelling in any solvents, being completely inert, having inherent fluorescence, and long-term thermal (up to 450oC) and mechanical stability. Therefore this project is timely, aiming to develop a nanodiamond-based platform for antimicrobial applications.

Experimental methods of the project are: (1) to investigate and improve the antimicrobial activities of unmodified and novel surface-modified nanodiamonds (NDs) against the model strains Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli, including multi-drug resistant clinical isolates; (2) to examine the potential of NDs in potentiating or restoring the activity of traditional antibiotics against resistant isolates; (3) to study the synergistic effect of NDs-antibiotics conjugates against multi-drug resistant bacteria. The unique properties of ND in combination with traditional antibiotics will generate new paradigms in antimicrobial research and application.

The Multidisciplinary collaboration will allow us to build a stronger team by providing complementary research skills and knowledge to each existing strength between Materials, Engineering, and Microbiology.

References:

  1. H. J. Kim, Diamond Nanogel-Embedded Contact Lenses Mediate Lysozyme-Dependent Therapeutic Release, ACS Nano 8 (2014) 2998.
  2. X. Wang et al, Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells, ACS Nano 8 (2014) 12151.
  3. Morrissey I, Oggioni MR, Knight D, Curiao T, Coque T, Kalkanci A, Martinez JL; BIOHYPO Consortium. Evaluation of epidemiological cut-off values indicates that biocide resistant subpopulations are uncommon in natural isolates of clinically-relevant microorganisms. PLoS One. 2014 Jan 23;9(1):e86669.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology

Techniques that will be undertaken during the project:

Outline plan

Detail

1. Surface modified nanodiamond particles (Engineering)

The synthesis, purification and surface modification of NDs will be studied at UoL. UoL has extensive experience in the surface functionalization of NDs, such as with hydrogenation, oxidation and conjugation; the novel protocols established will be utilised in this project.

2. Nanodiamond characterization (Engineering)

Material characterisation will be carried out including SEM, Raman, XPS and FTIR to understand the surface chemistry at UoL’s Advanced Microscopy Center.

3. Antibacterial activity evaluation (Microbial Genetics)

The model bacteria E. coli, K. pneumoniae and S. aureus will be cultured in liquid broth media plus the diamond material to assess minimum inhibitory concentrations under reference conditions. The bacteria will also be grown as biofilms and then exposed to the ND. Viability will be assessed using live/dead staining and confocal microscopy. Minimum biofilm eradication concentrations (MBEC) will also be determined.

Under biosafety 2+ conditions we will test antimicrobial features of nanomaterials also on multi-drug resistant K. pneumoniae and S. aureus isolates.

4. Synergy effect evaluation

(Microbial Genetics)

Using the assays described above, the possibility of NDs to potentiate or restore the activity of traditional antibiotics against resistant isolates by synergy will be evaluated. Synergistic effects of NDs-antibiotics conjugates against drug-resistant bacteria will be assessed.

Contact: Professor Haitao Ye, University of Leicester