Synthesis of Conductive Polymer Nanoparticles for use in Imaging and Assay Development

Lead Research Organisation: King's College London
Department Name: Physics

Abstract

Conjugated polymers (CPs) have emerged as promising materials for the production of fluorescent devices. They exhibit semiconducting behaviours as they have suitable and structure to allow conduction and the formation of excitons. They possess the ease of processing of plastics, and the electronic behaviour of metals and semiconductors. They have high quantum yields and extinction coefficients in solutions. They can be dissolved in a range of solvents depending on their functionality, and their chemical and physical characteristics can be finely tuned by changing the side groups. Due to their unique properties, it has been proposed that CPs could be used to synthesis nanoparticles that can be used in imaging and drug delivery systems.
This project aims to answer if nanoparticles can be synthesised from CPs, focusing on Poly(3-hexylthiophene-2,5-diyl) (P3HT), Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) and Cyano-Polyphenylene vinylene (CN-PPV). If nanoparticles can be synthesis, then the project will aim to address if the CPNs can be used in a Point of Care (POC) assay (as an initial proof of concept). Further development will be to take the CPNs forward for both a bioimaging and treatment application (i.e. can CPNs be used for theranostics).
The first step of the project will be to see if tuneable emission of the CPs can be achieved by a) Studying their characteristics in different solvents (solvatochromism) and b) If a change in the initial concentration of CPs affects emission. The goal will be to have a CP that can be tuned throughout the entire spectrum with narrow, distinct bands.
The second step of the project will be to take the most promising CP and determine if nanoparticles can be synthesised by simple aqueous methods (such as miniemulsion or nanoprecipitation). The project will look at both PEG as a surfactant to make the CPNs water soluble, and also using silica to form cores (or shells) surrounding the CPNs. A wide variety of experiments will be done to determine fluorescence viability and size of nanoparticles.
The third step of the project will to answer if the CPNs surface can be functionalised for antibody conjugation. This will involve testing different conjugation methods (such as adding a thiol or carboxyl group to the CP or silica shell), determining zeta potential of the shell and ultimately determining if antibody can be conjugated to the surface.
Finally, the project will address the question of can the CPNs be used in a POC assay. This will involve optimising and developing the immunoassay for studies with prostate/bowel cancer biomarkers or else bacterial growths in patients with impaired lung function.
By using CPs which can be synthesised with relatively simple aqueous chemistry, and are more biocompatible compared to heavy metal QDs, the ultimate goal is to translate the CPNs into an assay for proof of concept. This can then be taken forward as a potential theranostic application.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509498/1 01/10/2016 30/09/2021
1668373 Studentship EP/N509498/1 01/10/2015 31/03/2019 Struan Bourke
 
Title Nanoparticles trapped in glass 
Description Glass pieces, that shaped around a 3d printed mold of the structure of conjugated polymer which is then burnt out to leave behind a space which nanoparticles are added before the whole glass piece is merged together. 
Type Of Art Artwork 
Year Produced 2017 
Impact The glass pieces have been shown at a number of conferences and seminars. The purpose is to allow the public to easily visualise a system so small that you need very specialised equipment to see them. Glass is a truly wonderful material for using with objects that are colourful and fluoresce. 
URL http://www.shelleyjames.co.uk/
 
Description 1) That controlled oxidation of conjugated polymers can provide a full set of fluorescent particles that cover the entire visible spectrum. However, depending on how you coat these conjugated polymers, they can prove highly toxic to cells. This may be due to an oxygen stress effect on the cells, or a process we still haven't fully understood. 2) The type of polymer you use to form the nanoparticle, directly affects the physical characteristics of the nanoparticle (while the optical characteristics are still very dependent on the conjugated polymer) 3) Silica shelled nanoparticles are small, bright and very stable but at high concentration they have a negative effect on the cells. Functionalising the surface of silica is also difficult when you have such a large polymer inside. This work is still being developed. 4) One pot chemistry involving dialysis bags can provide a fast, easy method for higher yield of conjugated polymer nanoparticles.
Exploitation Route Conjugated polymers are wonderful for a number of different systems. Our findings could be taken forward easily for in vivo studies, as a large portion of the work was done in cells. Expanding on from this, you could start developing the surface of these nanoparticles for target specific binding as well as drug delivery system. As the work stands, these are excellent imaging agents that have strong brightness and good life-time.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description CR Barber Trust Fund
Amount £175 (GBP)
Organisation Institute of Physics (IOP) 
Sector Learned Society
Country United Kingdom
Start 01/2017 
End 01/2017
 
Description Conference Funds 2016/17
Amount £300 (GBP)
Organisation King's College London 
Department King's College London, Graduate School
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 01/2017
 
Description Otrewill International Travel Scholarship
Amount £1,000 (GBP)
Organisation Macro Group UK 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2018 
End 11/2018
 
Description "Conjugated Polymers-Particles for the Future" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact As part of Somerset House's "Utopia 2016: A Year of Imagination and Possibility" I gave a lunchtime talk to 50 people from the general public about how conjugated polymers have gathered great momentum in both the fields of Optics, as well as Biological Imaging. I discussed how they work, and how visualising them is difficult. I also said how that glass had provided a medium to show these.
Year(s) Of Engagement Activity 2016
URL http://www.craftscouncil.org.uk/listings/particles-for-the-future/
 
Description "The Physics of Life" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I was asked to be a speaker at the Institute of Physic's "The Physics of Life" which was open to the general public. It was a day of talking about how physics shapes life, as well as current work by a number of scientists.
Year(s) Of Engagement Activity 2017
URL https://www.events.iop.org/e/the-physics-of-life-124774189/page.html
 
Description Magazine article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact As part of a collaboration with a group of artists and the university's own "Wheatstone Lab", I was asked to write up in the departments magazine about the work that was done. I worked with a glass maker where we encased conjugated polymer nanoparticles in a 3-d printed structure. The purpose was to explain why it's important to involve non-scientist on projects to discuss with a wider audience.
Year(s) Of Engagement Activity 2016
URL https://www.reactiveplasmonics.org/wp-content/uploads/2017/02/NanostrandExport.pdf
 
Description School visit (Glasgow, Scotland) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 100 students aged 16-18 attended a talk about my career in STEM hosted by the school. Students were interested in what a degree ins science could do, how to apply to university degrees and where my field of research was going.
Year(s) Of Engagement Activity 2016
URL https://www.staloysius.org/aloysian-life/news/oa-inspires-science-students-with-career-talk-356