Functionalised semiconducting polymer nanoparticles for bioelectronic medicine
File(s)
Author(s)
Lo Fiego, Alessandra
Type
Thesis
Abstract
Semiconducting polymer nanoparticles (SPNs) are finding more and more biomedical applications. However, some challenges remain on the pathway towards clinical translation. These concern mainly physical/biological stability of the SPNs, their capability for active targeting and the reproducibility and scalability of their fabrication. In this thesis, a novel method for the synthesis of functionalised semiconducting polymer nanoparticles endowed with exceptional stability and specific cell targeting capability is presented.
The developed method is based on a facile synthetic route to PEGylated graft co-polymers via nucleophilic aromatic substitution (SNAr) between the fluorine on the BT unit of the polymer backbone and the terminal alcohol group of PEG derivatives. The simple nanoprecipitation of the synthesised PEG graft co-polymers in water yields SPNs with high colloidal stability in a selection of media and conditions, and long-circulation capability in zebrafish embryo models. The straightforward synthetic tuning of PEG length and PEG grafting density allows for the tuning of the antifouling properties of the SPNs.
The synthesis of PEG graft co-polymers with azide-terminated PEG derivatives affords the fabrication of SPNs that can be further functionalised with affinity ligands via click chemistry. This, combined with the site-specific modification of affinity ligands with bromo/dibromopyridazinedione-PEG-BCN linkers, enables the reproducible fabrication of SPNs capable of selective cell targeting both in vitro and in vivo. The synthetic tuning of azide density allows for the tuning of the final ligand density on the SPN surface.
The broad applicability of the presented method was demonstrated through the synthesis of a library of SPNs, covering the wavelength spectrum from the UV to the NIR. The possibility of tailoring and tuning all the components (semiconducting polymer core, PEG shells and biorecognition layer) renders the presented functionalised SPNs a versatile and modular platform that can be designed toward many different biomedical applications. In this thesis, fluorescent cancer imaging and optoelectronic cell stimulations are given as an example.
The developed method is based on a facile synthetic route to PEGylated graft co-polymers via nucleophilic aromatic substitution (SNAr) between the fluorine on the BT unit of the polymer backbone and the terminal alcohol group of PEG derivatives. The simple nanoprecipitation of the synthesised PEG graft co-polymers in water yields SPNs with high colloidal stability in a selection of media and conditions, and long-circulation capability in zebrafish embryo models. The straightforward synthetic tuning of PEG length and PEG grafting density allows for the tuning of the antifouling properties of the SPNs.
The synthesis of PEG graft co-polymers with azide-terminated PEG derivatives affords the fabrication of SPNs that can be further functionalised with affinity ligands via click chemistry. This, combined with the site-specific modification of affinity ligands with bromo/dibromopyridazinedione-PEG-BCN linkers, enables the reproducible fabrication of SPNs capable of selective cell targeting both in vitro and in vivo. The synthetic tuning of azide density allows for the tuning of the final ligand density on the SPN surface.
The broad applicability of the presented method was demonstrated through the synthesis of a library of SPNs, covering the wavelength spectrum from the UV to the NIR. The possibility of tailoring and tuning all the components (semiconducting polymer core, PEG shells and biorecognition layer) renders the presented functionalised SPNs a versatile and modular platform that can be designed toward many different biomedical applications. In this thesis, fluorescent cancer imaging and optoelectronic cell stimulations are given as an example.
Version
Open Access
Date Issued
2023-04-14
Date Awarded
01/06/2023
License URL
Advisor
Stevens, Molly M.
Sponsor
Engineering and Physical Sciences Research Council
Rosetrees Trust
Grant Number
Grant No. EP/ L016737/1
PhD2022/100002
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)