Bioinspired worm-like nanoparticles for the delivery of anti-cancer stem cell agents

Qualification: PhD

Department: School of Chemistry

Application deadline: 21st November 2019

Start date: 28th September 2020

Overview

Supervisors

Dr Kogularamanan (Rama) Suntharalingam and Dr Robert Britton

Project Description:

Cancer relapse and metastasis, the leading cause of cancer-associated deaths, is strongly linked to the existence of cancer stem cells (CSCs), a small sub-population of cancer cells defined by their ability to self-renew, differentiate, and form secondary tumours. Conventional chemotherapy and radiotherapy coupled with surgery effectively reduces primary tumour size by removing the bulk of cancer cells, however, CSCs can survive treatment and regenerate secondary tumours with higher metastatic propensity. To improve clinical outcomes, treatments must have the ability to eradicate the entire population of cancer cells, including CSCs, otherwise CSC-mediated relapse could occur. Although progress has been made in the identification of potential CSC therapeutic targets, there are still no clinically approved drug formulation that can completely remove CSCs. Part of the reason for this is the ineffective delivery of CSC-active agents to CSCs.

Nanoscale technologies offer a method to unambiguously deliver chemotherapeutics to their site of action. Nano-systems increase drug solubility, bioavailability, and extend drug half-life. Nanoparticles can passively target tumours by taking advantage of the enhanced permeability and retention (EPR) effect. Several nanoparticle formulations exist for drug delivery, including those based on iron oxide, carbon nanotubes, gold, liposomes, and polymers. Nanoparticles comprising of polymers are of particular interest due to their synthetic versatility and tuneable properties. Most polymer-based nanoparticles are spherical, however, biometric studies have shown that non-spherical constructs benefit from higher circulation times and drug loading. This project will develop “worm-like” nanoparticles (filomicelles), based on naturally occurring viruses like Ebola and Marburg, to delivery CSC-active agents to CSCs. The filomicelles will be made up of biocompatible and biodegradable polymers functionalised with different permutations and ratios of antibodies specific for receptors on the membrane of CSCs. This will enable pattern based recognition of CSCs, and facilitate safe, selective, and personalised delivery. The streamline nature of the filomicelles will also enable deeper penetration into tumours. As CSCs are thought to reside in deep tumour pockets, this approach could provide access to CSC microenvironments unlike current state-of-the-art nano-delivery systems. The long-term outcomes of this project will inform (and potentially revolutionise) the way cancer drugs are administered to patients.

References: 

1. Farokhzad OC, Langer R, “Impact of Nanotechnology on Drug Delivery” ACS Nano, 2009, 3, 16-20.

2. Oltra NS, Swift  J, Mahmud A, Rajagopal K, Loverde SM, Discher DE, “Filomicelles in nanomedicine – from flexible, fragmentable, and ligand-targetable drug carrier designs to combination therapy for brain tumors” Journal of Materials Chemistry B, 2013, 1, 5177-5185.

3. Truong NP, Quinn JF, Whittaker MR, Davis TP, “Polymeric filomicelles and nanoworms: two decades of synthesis and application” Polymer Chemistry, 2016, 7, 4295-4312.

4. Eskandari A, Boodram JN, Lu C, Bruno PM, Hemann M, Suntharalingam K, “The breast cancer stem cell potency of copper(II) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles” Dalton Transactions, 2016, 45, 17867-17873. 

5. Eskandari A, Suntharalingam K, “A reactive oxygen species-generating, cancer stem cell-potent manganese(II) complex and its encapsulation into polymeric nanoparticles”  Chemical Science, 2019, 10, 7792-7800

Funding

Funding

UK/EU applicants

This research project is eligible for a fully funded College of Science and Engineering studentship which includes:

A full UK/EU fee waiver for 3.5 years
An annual tax free stipend (For 2019/20 this is currently £15,009)
Research Training Support Grant (RTSG)

International Applicants

This project is eligible for a partially funded College of Science and Engineering studentship which includes:

A full UK/EU fee waiver for 3.5 years (applicants will need to provide evidence they can fund the difference between the UK/EU fee and International fee for the duration of their studies)
An annual tax free stipend of £15,009 (2019/20)
Research Training Support Grant (RTSG)

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject or overseas equivalent.

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

Project / Funding Enquiries: csepgr@le.ac.uk 

Application enquiries to pgradmissions@le.ac.uk

How to apply

How to apply

Please use the Apply button at the bottom of the page.
Select September 2020 entry.

Application Notes

We recommend you apply as early as possible so that any missing information can be obtained before the deadline.

In the funding section of the form state CSE2020 Suntharalingam Studentship

In the research proposal section include the name of the supervisors and project title.  If you are applying for more than one project within Chemistry include details of each project.

In the personal statement section upload your completed CSE Studentship Form.  If you are applying for more than one Chemistry project complete a form for each project and email the additional forms to csepgr@le.ac.uk together with your application ID number.  If you are applying for projects in other subject areas please submit separate PhD applications online.

Upload a copy of your CV, copies of your degree certificates and transcripts if awarded and evidence of English language proficiency if applicable and available.

If you already have reference letters please upload these. If not enter the contact details of your referees in the reference section. Please ask your referees if they can submit their references as quickly as possible, ideally within two weeks of receipt of our reference request.

Application timetable

21st November Deadline for applications and all supporting documents 
9th December Interview invitations to be sent out by email
w/c 13th January 2020 Interviews
21st January 2020 Informal offers to be made
31st January 2020 Deadline for acceptable of informal offers 

The PGR Admissions Office will notify unsuccessful applicants once a decision has been made.

Eligibility

Eligibility

UK/EU Applicants

International applicants who can demonstrate that they can fund the difference between UK/EU and International fees.