Conjugated Polymer Nanoparticles for Applications in Bioimaging

Abstract

Conjugated Polymer Nanoparticles for Applications in Bioimaging Conjugated polymer nanoparticles (CPNs) have been reported to have promising properties for use in bioimaging applications due to their high brightness, excellent photostability, non-blinking and low toxicity. However, conjugated polymers are normally insoluble in water due to the hydrophobic nature of the polymer backbone. To overcome this issue, introduction of surfactant to the heterogeneous phase or charge group onto the polymer backbone can improve the solubility of conjugated polymer. CPNs can be prepared from preformed polymer (precipitation and miniemulsion of preformed polymers) or the polymerisation of monomers inside nano scale droplets (miniemulsion polymerisation). These techniques often require the use of surfactants to stabilise the nanoparticles in aqueous phase. However, there is no report on the preparation of CPNs via surfactant free miniemulsion polymerisation to date yet which draw our interest to propose the hypothesis that introduction of surfactant like monomer into the preparation of CPNs by miniemulsion polymerisation would stabilise the miniemulsion during polymerisation process. This thesis reports the development of new synthetic methods to prepare polyfluorene based conjugated polymer nanoparticles (CPNs) via surfactant free miniemulsion polymerisation and to investigate the use of these CPNs for biological imaging. In chapter 3, to address the hypothesis that introducing charge group onto the polymer chains can facilitate preparation of CPNs via surfactant free miniemulsion polymerisation, sulfate functional group was introduced to the side chain of dibromo fluorene monomer via the side chain attachment on the 9-position of carbon atom on the fluorene monomer to mimic the surfactant like structure. The sulfate fluorene monomer was then used in preparation of green emitting fluorene based CPNs via Suzuki cross-coupling surfactant free miniemulsion polymerisation. The functionalised nanoparticles can be prepared without the use of surfactant under surfactant free conditions with photoluminescence quantum yield (PLQY) values of up to 63% in water. The nanoparticle size could be readily controlled by modifying the sonication time used to prepare the miniemulsion ranging from 188 nm to 90 nm. The nanoparticles were dispersed in water at different pH range from acidic to basic conditions (pH of 3 to 9) and stable over one-year storage. In chapter 4, the outcome of chapter 3 draw our interest to further incorporation of carboxylic acid group into fluorene monomer. The carboxylic acid was introduced into the 9-position of the carbon on the fluorene monomer to mimic the role of surfactant and further allow the attachment of bio-molecule via bioconjugation method. A similar approach for preparation of green emitting CPNs in chapter 3 was used in this chapter. The carboxylic acid functionalised green emitting nanoparticles can be prepared without the use of surfactant under surfactant free conditions with photoluminescence quantum yield (PLQY) values of up to 65% in water. The effect of the sonication time on the size of particles has been investigated. Longer sonication time reduce the size of nanoparticles from a diameter of 175 nm to 90 nm. The composition of the nanoparticles also affects the size and optical properties of the nanoparticles. The colloidal stability of the nanoparticles was determined in pH range 3 to 9 and the nanoparticles stable in neutral and basic aqueous medium (pH > 6), and stable over one-year storage. The carboxylic acid on the side chain of nanoparticles can be reacted with primary amines using EDC.HCl and Sulfo-NHS activating agents. This allow the nanoparticles to couple to biomolecules for application in bioimaging. In chapter 5, the ability of carboxylic acid functionalised CPNs to form amide bond with water miscible primary amine (n-butylamin) and great colloidal stability of the CPNs in water media for a long

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Michael Turner (Supervisor) & Michelle Webb (Supervisor)