Phosphonate-anchored ligands for upconversion imaging nanoprobes
File(s)
Author(s)
Midson, Megan Olga
Type
Thesis
Abstract
Upconversion nanoparticles (UCNPs) are a lanthanide-doped inorganic nanomaterial which absorb near-infrared radiation and emit visible light. For the last 20 years, researchers have been interested in using UCNPs as biomedical imaging agents. Their unique optical properties make them suitable for imaging within tissue, with UCNPs exhibiting resistance to photobleaching and having long luminescence lifetimes.
In this work, novel UCNP-ligand systems were synthesised. Phosphonate ligands were designed and synthesised with the aim of achieving particular physical or photophysical properties. Work in this thesis begins with studying the interaction between the upconversion nanomaterial NaYF4:Yb,Er and the bound surface ligands. The stability of the nanoparticle-ligand interaction in an imaging agent in vivo determines the resistance to aggregation. The results presented in this work show bisphosphonic acids bind more strongly to the surface of UCNPs than carboxylic acids and this was determined by 1H NMR spectroscopy and by dynamic light scattering (DLS).
Analyte sensing in vivo has the potential to provide information about biological systems in both healthy and disease environments. Phosphonate functionalised, pH-sensitive rhodamine ligands were synthesised and appended to the surface of UCNPs to create UCNP-based pH nanosensors. The nanoprobes were phase transferred using water soluble PEG-bisphosphonate ligands. It was found that poor emission intensity of UCNPs in aqueous systems was a common issue. To mitigate this, sensitizing cyanine ligands were synthesised. Nanosystems of NaYF4:Yb,Er UCNPs functionalised with cyanines were assembled and emission enhancement in these systems was achieved.
In the past few years, there has been increasing interest in the synthesis of multimodal imaging agents. Finally, MR functionality was introduced to the nanoparticle imaging agents. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and various attempts were made at synthesising dual-modal MR/optical imaging agents by creating core-shell SPIONs-UCNP imaging agents.
In this work, novel UCNP-ligand systems were synthesised. Phosphonate ligands were designed and synthesised with the aim of achieving particular physical or photophysical properties. Work in this thesis begins with studying the interaction between the upconversion nanomaterial NaYF4:Yb,Er and the bound surface ligands. The stability of the nanoparticle-ligand interaction in an imaging agent in vivo determines the resistance to aggregation. The results presented in this work show bisphosphonic acids bind more strongly to the surface of UCNPs than carboxylic acids and this was determined by 1H NMR spectroscopy and by dynamic light scattering (DLS).
Analyte sensing in vivo has the potential to provide information about biological systems in both healthy and disease environments. Phosphonate functionalised, pH-sensitive rhodamine ligands were synthesised and appended to the surface of UCNPs to create UCNP-based pH nanosensors. The nanoprobes were phase transferred using water soluble PEG-bisphosphonate ligands. It was found that poor emission intensity of UCNPs in aqueous systems was a common issue. To mitigate this, sensitizing cyanine ligands were synthesised. Nanosystems of NaYF4:Yb,Er UCNPs functionalised with cyanines were assembled and emission enhancement in these systems was achieved.
In the past few years, there has been increasing interest in the synthesis of multimodal imaging agents. Finally, MR functionality was introduced to the nanoparticle imaging agents. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and various attempts were made at synthesising dual-modal MR/optical imaging agents by creating core-shell SPIONs-UCNP imaging agents.
Version
Open Access
Date Issued
2021-06
Date Awarded
2021-09
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Long, Nicholas
Sponsor
Engineering and Physical Sciences Research Council (EPSRC)
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)