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Ultrabright drug nanocarriers for advanced theragnostics and happy aging


Project Description

Supervisors; Antonios Kelarakis, Marta Krysmann, Claire Mellor, Professor Xuhong Guo

The development of a new generation of highly PL, yet non-toxic and cost-effective nanoemitters that offer simultaneously advanced bioimaging coupled with supreme drug delivery capabilities, thoroughly inaccessible with current technologies.

Hypothesis

C-dots surface decorated with cell-permeating peptides exhibit enhanced cell uptake and drug delivery performance, without compromising their non-toxic character and their supreme PL properties. Our preliminarily data provides strong evidence about the validity of our hypothesis.

Methodology

First, C-dots will be synthesised based on controlled pyrolytic treatments of suitable molecular precursors as described by our group in a series of reports1-7. The synthetic protocol eliminates the use of toxic solvents and is thoroughly compatible with green chemistry practices. Size separation strategies (mainly centrifuge and dialysis) will be employed to generate well-defined nanoparticles. Second, the nanoparticles will be surface-functionalised with cell-permeating peptides (a series of suitable sequences will be synthesized and purified in our labs) in order to improve their selectivity, biocompatibility and their cell uptake performance. Solid-phase peptide synthesis will take place by means of an automated single-channel synthesizer and the product will be purified via HPLC. Third, bioactive compounds (in the first instance, emphasis will be given to antineoplastic drugs) will be attached to peptide/C-dots via covalent coupling and other complexation strategies (e.g. electrostatic forces, π-π interactions, etc). Fourth, the peptide/C-dots conjugates and their drug loaded counterparts will be thoroughly characterised (in terms of size, surface chemistry, hydrodynamic behaviour, photoluminescence) and will systematically assessed with respect to their toxicity, bioimaging and drug delivery capabilities.

To that end, Professor Guo’s team will oversee a detailed study on the structure and dynamics of those systems, combing X-ray synchrotron data with advanced mathematical modelling.

Applications

Applicants must apply using the online form on the University Alliance website at https://unialliance.ac.uk/dta/cofund/how-to-apply/. Full details of the programme, eligibility details and a list of available research projects can be seen at https://unialliance.ac.uk/dta/cofund/

The final deadline for application is 12 April 2019.

Funding Notes

DTA3/COFUND participants will be employed for 36 months with a minimum salary of (approximately) £20,989 per annum. Tuition fees will waived for DTA3/COFUND participants who will also be able to access an annual DTA elective bursary to enable attendance at DTA training events and interact with colleagues across the Doctoral Training Alliance(s).

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 801604.

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