Development of Novel Theranostic Contrast Agents for Magnetic Resonance Imaging (MRI)

Description

The aim of this PhD project is to develop novel nanoparticulate theranostic agents for use in targeted drug delivery, monitored by Magnetic Resonance Imaging (MRI). Theranostic agents are hybrid nanoparticle structures that combine both therapeutic and diagnostic components. Nanomedicine offers the potential to create nanocarrier materials which can incorporate both therapeutic drug molecules and diagnostic imaging agents in their structures. Such advanced material research would allow for disease site specific drug delivery and monitoring of the disease during and following therapeutic intervention, accelerating the transition from conventional medicine towards personalised, precision medicine.

MRI operates similarly to having a proton NMR experiment carried out on the human body. MRI visualises water protons due to their high abundance in biological systems. Contrast agents are the MRI equivalent of a dye, increasing proton relaxation rates of water molecules within their vicinity. It is not the contrast agent per se which is seen in the image, rather its effect on the longitudinal relaxation (T1) and transverse relaxation (T2) of surrounding water proton nuclei. T1 relaxation rate enhancement is achieved by the introduction of chelates containing paramagnetic ions, such as (Gadolinium (III)), while T2 relaxation rate enhancement is achieved through use of superparamagnetic agents, such as superparamagnetic iron oxide nanoparticles (SPION). Nanomedicine offers the potential to develop organic nanocarrier particles that can incorporate both therapeutic drug molecules as well as MRI contrast agents. Through tailored synthesis, such nanocarriers can be targeted to various physiological sites and accumulated within various cell types and intracellular locations depending on particle structural and chemical properties.

The aim of the project is to incorporate both inorganic imaging agents and organic cancer drug molecules (e.g. doxorubicin) into organic/polymeric nanoparticle structures to generate novel cancer drug nanocarriers with MRI functionality. The polymers themselves will be synthesised through a range of polymerisation techniques (e.g. ATRP, RAFT) to be amphiphilic in nature. As such, upon addition to water the amphiphilic properties would cause polymers to self-assemble to form organic nanoparticle structures, which will encapsulate organic drug molecules within the hydrophobic core. MRI functionality will be incorporated either through further encapsulation of SPIONs in the polymer particle core, or polymer particles synthesised to possess Gd(III) chelates on their surface.

This studentship is truly multidisciplinary across a broad range of areas: polymer, organic and inorganic synthesis and characterisation. The project will be based within the Department of Chemistry at the University of Liverpool and will interact with multidisciplinary scientists across the wider Nanomedicine Partnership and the Functional Materials Team. Furthermore, the project will be aided through collaboration with the UoL Centre of Preclinical Imaging (CPI, Prof Harish Poptani), thus will benefit from the use of MRI equipment unique at UoL. Thus, the PhD studentship will receive training in developing cell cultures, biological assays and in vivo studies.

For any enquiries please contact Dr Marco Giardiello on 

To apply for this opportunity please visit: https://www.liverpool.ac.uk/study/postgraduate-research/how-to-apply/ In your online application please quote reference CCPR005 in the finance section. Please note if you have not heard from us by March 12th 2021 then you have not been successful on this occasion.

Availability

Open to students worldwide

Funding information

Funded studentship

The funding for this position is from an EPSRC DTP studentship. The eligibility details of both are below.
EPSRC eligibility: Applications from candidates meeting the eligibility requirements of the EPSRC are welcome – please refer to the EPSRC Website. The award will pay full tuition fees and a maintenance grant for 3.5 years. The maintenance grant is £15,285 pa for 2021/22, with the possibility of an increase for 2022/23

Supervisors

References

Stable, polymer-directed and SPION-nucleated magnetic amphiphilic block copolymer nanoprecipitates with readily reversible assembly in magnetic fields. Giardiello, M., Hatton, F. L., Slater, R. A., Chambon, P., North, J., Peacock, A. K., He, T., McDonald, T. O., Owen, A., Rannard, S. P. Nanoscale, 8, 7224-7231 (2016)
pH-Responsive Lanthanide Complexes Based on Reversible Ligation of a Diphenylphosphinamide. Giardiello, M., Botta, M., Lowe, M. P., Inorganic Chemistry, 52 (24), 14264 – 14269 (2013)
Facile synthesis of complex multi-component organic and organic–magnetic inorganic nanocomposite particles. Giardiello, M., McDonald, T. O., Smith, D., Martin, P., Owen, A., Rannard, S.P. Journal of Materials Chemistry, 22 (47), 24744 - 24752 (2012)
Cell Permeable Ln (III) Chelate Functionalized InP Quantum Dots as Multimodal Imaging Agents. Stasiuk, G.J., Tamang, S., Imbert, D., Poillot, C., Giardiello M., Tisseyre, C., Barbier, E. L., Fries, P., H., de Waard, M., Reiss, P., Mazzanti. M., ACS Nano, 5 (10), 8193 – 8201 (2011)
Synthesis of lanthanide(III) complexes appended with a diphenylphosphinamide and their interaction with human serum albumin. Giardiello, M., Botta, M., Lowe, M. P., Journal of Inclusion Phenomena and Macrocyclic Chemistry, 71 (3-4), 435-444 (2011)
A luminescence study of Eu(III) analogues of esterase-activated magnetic resonance contrast agents. Giardiello, M. Lowe, M. P., Inorganic Chemistry 48 (17), 8515 – 8522 (2009)
An esterase-activated magnetic resonance contrast agent. Giardiello, M., Lowe, M. P., Botta, M., Chemical Communications, 4044 – 4046 (2007)