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Designer nanoparticles: optimising shape and size for targeted nanoscale drug delivery


   Birmingham and Melbourne Joint PhDs

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  Prof R O'Reilly  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

Birmingham United Kingdom Polymer Chemistry

About the Project

Nanoparticles (NPs) are a promising strategy for improving the clinical outcomes for a range of diseases, by improving drug efficacy through enhanced delivery and uptake into disease sites.1 To ultimately advance drug delivery nanoparticles into clinical stages, it is important to carefully consider NP properties such as size, chemistry and functionality, and how these parameters influence drug delivery performance.2 In particular, particle shape is a vital design parameter for realising the next generation of NPs. Traditional drug delivery nanoparticles have been spherical structures, however more recently anisotropic nanoparticles (non-spherical) have shown very different behaviour in the body from their spherical counterparts, leading to a whole host of physical, chemical and biological effects otherwise inaccessible.3 The dimensions of a polymer particle have implications on cellular uptake behaviour, circulation lifetimes, extravasation through tissues and distribution in vivo. With the inclusion of targeting ligands to achieve specific cellular interactions, these interactions become even more complex.4 It is therefore crucial that we fully understand how these NP properties impact biological behaviours, however fundamental studies in this regard are often incomplete or restricted to few available NPs.

The aim of this studentship is therefore to engineer nanoparticles of varying shapes and sizes, further featuring ligands for active cellular targeting, and investigate the influence on various biological behaviours. To achieve this, the student will work within two diverse and interdisciplinary teams across the world-class facilities of the University of Birmingham (UoB) School of Chemistry and University of Melbourne (UoM) Department of Chemical Engineering. Nanoparticles of varying shapes and sizes (spheres, cylinders, 2D platelets) will be synthesised at UoB through Crystallization-Driven Self Assembly, further modified to feature dyes for biological evaluation. Modifications of the NPs to feature active targeting ligands will be achieved through the research period at UoM.

The biological behaviours of the varying NPs will be tested in a range of in vitro systems, making use of facilities at both UoB and UoM. In the later stages of the project, the ability for well-performing NPs to be exploited for therapeutic applications will be assessed through the inclusion of drugs or other active molecules.

During the project, the PhD student will develop skills in research and writing literature; developing and characterising nanoparticles; tissue culture techniques to test the in vitro efficacy of the technology in physiologically relevant environments. Techniques likely to be used during the PhD include small molecule synthesis; nanoparticle preparation; chemical characterisation; dynamic light scattering; tissue culture and microscopy.

We are looking for a motivated and enthusiastic applicant with a willingness to engage in interdisciplinary and translational research. The studentship is open to applicants from a range of backgrounds (e.g. biology, chemistry, engineering).


Funding Notes

A fully-funded studentship, which includes tax-free Doctoral Stipend of £15,609* per annum, tuition fees and provision for a return trip to Birmingham/Melbourne is available for Home/EU and Overseas students on this Joint PhD programme between the University of Birmingham and the University of Melbourne for October 2021 start.
*subject to inflationary variation, with a comparable rate for students who are to be hosted by the University of Melbourne.

References

(1) Pearce, A. K.; O’Reilly, R. K. Insights into Active Targeting of Nanoparticles in Drug Delivery: Advances in Clinical Studies and Design Considerations for Cancer Nanomedicine. Bioconjug. Chem. 2019, 30 (9), 2300–2311. https://doi.org/10.1021/acs.bioconjchem.9b00456.
(2) Cui, J.; Richardson, J. J.; Björnmalm, M.; Faria, M.; Caruso, F. Nanoengineered Templated Polymer Particles: Navigating the Biological Realm. Acc. Chem. Res. 2016, 49 (6), 1139–1148. https://doi.org/10.1021/acs.accounts.6b00088.
(3) Meyer, R. A.; Green, J. J. Shaping the Future of Nanomedicine: Anisotropy in Polymeric Nanoparticle Design. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016, 8 (2), 191–207. https://doi.org/10.1002/wnan.1348.
(4) Song, D.; Cui, J.; Ju, Y.; Faria, M.; Sun, H.; Howard, C. B.; Thurecht, K. J.; Caruso, F. Cellular Targeting of Bispecific Antibody-Functionalized Poly(Ethylene Glycol) Capsules: Do Shape and Size Matter? ACS Appl. Mater. Interfaces 2019, 11 (32), 28720–28731. https://doi.org/10.1021/acsami.9b10304.
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