About the Project
The Kamaly group (https://www.imperial.ac.uk/people/nazila.kamaly) uses bioinspired approaches to create multi-functional nanoparticles capable of changing their surface or core properties in response to local or up-regulated disease markers for more effective and smart stimuli-responsive drug delivery. In this manner, potent biological therapeutics (such as enzymes) can be delivered in a spatiotemporally controlled manner, with the aim of reducing enzyme degradation, systemic toxicity and collateral damage to the host. In particular we are interested in the synthesis of nanogels with diverse properties that can be designed to facilitate ‘smart’ drug delivery in response to up-regulated disease biomarkers.
Nanogels are nanometer-sized nanoparticles that have the ability to retain high volumes of water or biological fluids, and maintain their structure. This excellent and unique property makes them an ideal nanoplatform for the delivery of biological drugs such as enzymes. Nanogels have superior properties as they offer: 1) encapsulation stability for biologically sensitive payloads, 2) they have low immunogenicity and toxicity, and can be designed to be fully biodegradable, 3) multiple biological payloads can be delivered in a single nanogel, facilitating combination therapies, 4) their synthesis can be aqueous based and easily scaled, and 5) they are soft nanoparticles that can easily squeeze through restricted sites under haemodynamic sheer flow.
Nanogels are prepared via the heterogeneous polymerisation of monomers or precursors by either chemical or physical cross-linking. Furthermore, nanogels can be created to be responsive to a wide variety of environmental stimuli such as enzymes, temperature, pH and ionic strength. They are extremely versatile since these functionalities can be bestowed within their monomer design. This strategy of triggered disintegration makes cross-linked polymeric nanogels a promising system for the controlled delivery of biologics.
Project aim
According to the WHO, each year, 17.9 million people die from cardiovascular diseases (CVDs), mostly due to heart attacks and stroke – with CVDs accounting for 31% of all deaths worldwide, making this disease the number 1 cause of death globally. This project aims to develop novel nanogel therapies for catalytic pharmacological thrombolysis in the event of acute myocardial infarctions (heart attacks), whereby blood clots that block arteries can rapidly be broken down due the action of locally delivered enzymes. This new strategy aims to develop an intelligent drug delivery system that can precisely target the thrombus (blood clot that forms in vessels and remains there). The project will involve the synthesis of nanogels for the delivery of fibrinolytic enzymes. In the first instance monomer libraries (that will allow stimuli-responsive release of enzymes) will be synthesized and characterized, and applied to nanogel synthesis using polymerisation in confined droplets. Depending on their level of skills and interest, the student may also carry out experiments to test the biological efficacy of the nanogels. The project would be suitable for candidates with a synthetic chemistry background, interested in pursuing a PhD within a highly multidisciplinary environment.
Studentships are fully funded starting 1st October 2019. Applicants from the UK and EU are eligible for a full award (which includes full university fees and a maintenance allowance).
Applications must be submitted as one pdf file containing all materials to be given consideration. The file should include:
• A cover letter describing your motivation (1 page)
• Curriculum vitae
• Details of 2 academic referees
The ideal candidate should hold a Master level degree in synthetic chemistry, polymer chemistry or a related field. The applicant should have a strong academic record, be fluent in English, with excellent communication skills, and interested in working within a collaborative and cross-disciplinary environment.
To find out more please get in touch with Dr. Nazila Kamaly via email: [Email Address Removed]
Applications should be made through the College application form, which can be found at: https://www.imperial.ac.uk/study/pg/apply/how-to-apply/apply-for-a-research-programme-/
no later than August 15th 2019.
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