Polymer-QD hybrid nano-theranostics for Glioblastoma Multiforme treatment

The main aim of this PhD will be to develop an alternative approach for the design and manufacture of a therapeutic drugs systemic co-delivery system for Glioblastoma Multiforme (GBM), hence enhancing the efficiency of currently used standard poor soluble drugs applied in GBM therapy. This will be achieved by employing nanoscale CQDs, forming a nano-capsule with the therapeutics drugs by Layer-by-Layer assembly (LbL) for targeted drug delivery imaging. The process of LbL is ensuring that a nano-coating layer will embed the anticancer drugs and then provide transport and subsequent controlled release of the drug once at the target site.

This PhD will involve many different stages to achieve an overall new therapeutic target. The first stages will be to understand how therapeutic delivery systems work, how they work for cancer cells and to establish which therapeutic drugs are needed for targeting these cancerous tumour cells. This will help to give an overall molecular map and therapeutic strategy of the disease. Following this, the next stage will be to understand fully how CQDs form. This will require research into the properties of CQDs derived from carbon-based material that are desirable for the use in therapeutic drug delivery. Tests will be performed to determine the most efficient and high yielding way to obtain CQDs, such as from biomass waste, should this be the method which generates CQDs in the most facile, cheapest safest way. Several tests will be performed on the CQD product to ensure they are appropriate for moving forward, which include SEM-EDX, TEM, FTIR, TGA, XRD, XPS, BET, AFM, which are an array of testing techniques in order to characterise and optimise the fabrication conditions, while the gas and condensed liquid products will be analysed using GC and GC/MS (on-line for gas and off-line for liquid).

The porous carbon material generated will be modified with different chemicals to give optimised desired properties and better mechanical strength. The functionalised material will be characterised and optimised based on pore size analysis using the BET, carbon-nitrogen-hydrogen-sulphur content using the CNHS analyser, material morphology and structure using the FE-SEM, XRD, FTIR, XPS and Raman Spectroscopy methods. The electrochemical properties will be characterised in electrochemical cells for testing their capacitance and electrochemical activities.

Following this, LbL assembly will be studied and the reasons that it overrides previously used attempts at generating deposited multilayers will be established. This will enable functionalisation of the drug delivery system at the nanoscale. This will help to understand how they'd form a shell around the specific therapeutic drugs. This will require understanding the chemical interactions/ bonds that arise between the CQDs and the chemical sites/structure of the drug molecules. Once this is determined, the CQDs and the therapeutic drugs can be reacted together to give the overall structure necessary for a drug delivery system.

From the analysis of the background and the current state of the art of the field, this PhD project will give an answer to the following research questions:
1. Understand the luminescence of the CQDs and how difference in wavelength/ colour will affect the nanotheranostics
2. How to release the drugs from the nano-capsule/ controlled release i.e. successfully and not too early
3. The use of different cancer drugs, will study whether the CQDs will have to differ in terms of functional groups
4. Will Protecting Group Chemistry be needed for the transport of the drugs?
5. Study the effect of CQDs on the healthy and tumoral human cells
6. Imaging of the GBM cancer area
7. Biological Barriers Reaction, need to see the route that the nanotheranostics will take
8. How is the therapeutic delivery affected by the bloodstream?
9. How to expand the lifetime of the CQDs