Metal-mediated self-assembly of supramolecular coordination complexes (SCCs) has been explored, among other areas of potential usage, for biological applications. Indeed, metallosupramolecular systems have been shown to possess a plethora of interesting chemical-physical properties, as well as host-guest interactions, which make them suitable for molecular recognition and encapsulation of a variety of organic and inorganic guest molecules. Concerning biological studies, SCCs have been found to interact with DNA, possess anticancer activity, and function as drug-delivery vectors. The advantages of SCCs over other inorganic and hybrid porous materials, for example, molecular organic frameworks (MOFs), include being well-defined and discrete molecular entities with increased solubility in biological media.
Recently our group developed exo-functionalized Pd2L4(L= ligand) cages able to encapsulate the anticancer drug cisplatin (Schmidt et al., Chem. Eur. J., 2016) which also showed poor toxicity in healthy liver tissues. Drug encapsulation was proven by different methods, and the biological properties were investigated in cancer cells also with the aid of fluorescence microscopy. Based on these promising results we aim at further developing supramolecular self-assembled metallocages of Pd, but also of other transition metals (e.g. Au, Pt). Exo-functionalization with amino and hydroxyl moieties, among others, will be pursued, because it may be exploited for further conjugation of the cages to targeting moieties (e.g. peptides and antibodies) or to fluorescence tags.
The project will involve synthesis of the ligands and of the metallocages, characterization via a number of spectroscopic techniques, mass spectrometry and X-ray diffraction analysis. Moreover, the metallocages will be tested for their anticancer effects and drug delivery properties in cancer cells in vitro, alone and in combination with selected anticancer drugs. The drug encapsulation and release properties will also be studied in detail via spectroscopic and spectrometric techniques, as well as by fluorescence microscopy.
Bioconjugation of the metallocages to peptides, proteins and antibodies will also be performed and the products characterized by mass spectrometry. Coupling of the metallocages to gold nano-objects will also be attempted to improve the targeting to cancer tissues by enhancing the EPR effect of the conjugates.
Supervisors: Prof. Angela Casini http://www.cardiff.ac.uk/people/view/104658-casini-angela
Start date: 1 April 2016
Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a 2:1 degree or higher in a relevant subject, such as Pharmaceutical Sciences, or Chemistry.
Applications are particularly welcome from can candidates with:
• a Master’s degree in Medicinal and/or Inorganic Chemistry;
• experience in inorganic synthesis and characterisation of organic/inorganic molecules;
• understanding of chemistry and challenges in drug design; and
• a strong interest in medicinal chemistry.
Knowledge of biological characterisation techniques will represent an advantage.
This studentship consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,057 p.a. for 2015/16, updated each year).
One studentship is available.
Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students without further restrictions.
Consideration is automatic on applying for the PhD in Chemistry, with any future start date, via Cardiff University's Online Application Service. In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from the School. Please also provide a personal statement, CV, contact details of at least 2 academic referees, and please quote reference number in your application.
The deadline for applications is 20 February 2015.
Cardiff University reserves the right to close applications early should sufficient applications be received.
How good is research at Cardiff University in Chemistry?
FTE Category A staff submitted: 23.00
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