Responsive lanthanide-doped nanoparticles for bioimaging
With recent advances in nanotechnology, the tailored synthesis of functional nanoparticles has emerged as a new frontier for biomedical diagnostics, especially in the field of (pre-)clinical bioimaging. In this thesis, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) and Gd3+-doped...
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| Format: | Abschlussarbeit |
| Sprache: | English |
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2023
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| _version_ | 1826312159371460608 |
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| author | Yuan, D |
| author2 | Davis, J |
| author_facet | Davis, J Yuan, D |
| author_sort | Yuan, D |
| collection | OXFORD |
| description | With recent advances in nanotechnology, the tailored synthesis of functional nanoparticles has emerged as a new frontier for biomedical diagnostics, especially in the field of (pre-)clinical bioimaging. In this thesis, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) and Gd3+-doped mesoporous silica nanoparticles (Gd-MSNs) have been investigated as versatile, stimuli-responsive magnetic resonance imaging (MRI) contrast agents (CAs). One of the principal aims was to optimise <em>T</em>1 relaxivities (<em>r</em>1) for these paramagnetic nanoparticles, with a distinct emphasis on exploiting the often overlooked outer-sphere (OS) relaxation pathway. Another key objective was to design <em>T</em>1-active CAs whose OS relaxivities could be tuned in response to biologically-relevant stimuli (e.g., environmental pH), enabling disease-specific reporting capability by MRI. Following an introduction to the fundamental theory/project aims in <strong>Chapter 1</strong>, and a discussion of detailed synthetic/characterisation procedures (<strong>Chapter 2</strong>), the research results are presented in <strong>Chapters 3, 4</strong> and <strong>5</strong>. In <strong>Chapter 3</strong>, strategies for enhancing <em>T</em>1 contrast using Gd-MSNs are discussed. This enhancement is achieved by incorporating strong hydrogen-bonding acceptors (HBAs) into the channel sidewalls, influencing the mobility of the internalised water and hence amplifying OS relaxivities. This chapter also introduces a novel, one-pot Ugi-coupling reaction for the synthesis of bifunctional MSNs with dual-modal MRI and fluorescence imaging capabilities. In <strong>Chapter 4</strong> it is shown that externally grafting a pH-responsive, hydrophilic polymer onto Gd-MSNs results in a powerful <em>T</em>1 contrast agent which possesses the highest reported <em>r</em>1 switches at clinically-relevant magnetic fields (1.4 T, 1.5 T and 3 T). These ultrahigh switches result from modulating the mobility of nanoconfined water, and consequently the OS relaxivities, through a conformational change of the polymer. Building on this polymer-mediated OS mechanism, <strong>Chapter 5</strong> describes polymer-modified SPIONs possessing significant, reversible <em>r</em>1 switching, along with antifouling characteristics. <strong>Chapter 6</strong> summarises the conclusions from <strong>Chapters 3 - 5</strong>. <strong>Chapters 7</strong> and <strong>8</strong> provide relevant supplementary information and a list of references. |
| first_indexed | 2024-03-07T08:23:25Z |
| format | Thesis |
| id | oxford-uuid:8cf2e921-64e9-4b4a-ae1d-2c1cd7700160 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:23:25Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:8cf2e921-64e9-4b4a-ae1d-2c1cd77001602024-02-09T08:46:07ZResponsive lanthanide-doped nanoparticles for bioimagingThesishttp://purl.org/coar/resource_type/c_db06uuid:8cf2e921-64e9-4b4a-ae1d-2c1cd7700160NanotechnologyMagnetic resonance imagingRare earthsBioimagingMultimodal bioimagingLanthanidesInorganic chemistryEnglishHyrax Deposit2023Yuan, DDavis, JFaulkner, SKovacs, DEllis, CWith recent advances in nanotechnology, the tailored synthesis of functional nanoparticles has emerged as a new frontier for biomedical diagnostics, especially in the field of (pre-)clinical bioimaging. In this thesis, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) and Gd3+-doped mesoporous silica nanoparticles (Gd-MSNs) have been investigated as versatile, stimuli-responsive magnetic resonance imaging (MRI) contrast agents (CAs). One of the principal aims was to optimise <em>T</em>1 relaxivities (<em>r</em>1) for these paramagnetic nanoparticles, with a distinct emphasis on exploiting the often overlooked outer-sphere (OS) relaxation pathway. Another key objective was to design <em>T</em>1-active CAs whose OS relaxivities could be tuned in response to biologically-relevant stimuli (e.g., environmental pH), enabling disease-specific reporting capability by MRI. Following an introduction to the fundamental theory/project aims in <strong>Chapter 1</strong>, and a discussion of detailed synthetic/characterisation procedures (<strong>Chapter 2</strong>), the research results are presented in <strong>Chapters 3, 4</strong> and <strong>5</strong>. In <strong>Chapter 3</strong>, strategies for enhancing <em>T</em>1 contrast using Gd-MSNs are discussed. This enhancement is achieved by incorporating strong hydrogen-bonding acceptors (HBAs) into the channel sidewalls, influencing the mobility of the internalised water and hence amplifying OS relaxivities. This chapter also introduces a novel, one-pot Ugi-coupling reaction for the synthesis of bifunctional MSNs with dual-modal MRI and fluorescence imaging capabilities. In <strong>Chapter 4</strong> it is shown that externally grafting a pH-responsive, hydrophilic polymer onto Gd-MSNs results in a powerful <em>T</em>1 contrast agent which possesses the highest reported <em>r</em>1 switches at clinically-relevant magnetic fields (1.4 T, 1.5 T and 3 T). These ultrahigh switches result from modulating the mobility of nanoconfined water, and consequently the OS relaxivities, through a conformational change of the polymer. Building on this polymer-mediated OS mechanism, <strong>Chapter 5</strong> describes polymer-modified SPIONs possessing significant, reversible <em>r</em>1 switching, along with antifouling characteristics. <strong>Chapter 6</strong> summarises the conclusions from <strong>Chapters 3 - 5</strong>. <strong>Chapters 7</strong> and <strong>8</strong> provide relevant supplementary information and a list of references. |
| spellingShingle | Nanotechnology Magnetic resonance imaging Rare earths Bioimaging Multimodal bioimaging Lanthanides Inorganic chemistry Yuan, D Responsive lanthanide-doped nanoparticles for bioimaging |
| title | Responsive lanthanide-doped nanoparticles for bioimaging |
| title_full | Responsive lanthanide-doped nanoparticles for bioimaging |
| title_fullStr | Responsive lanthanide-doped nanoparticles for bioimaging |
| title_full_unstemmed | Responsive lanthanide-doped nanoparticles for bioimaging |
| title_short | Responsive lanthanide-doped nanoparticles for bioimaging |
| title_sort | responsive lanthanide doped nanoparticles for bioimaging |
| topic | Nanotechnology Magnetic resonance imaging Rare earths Bioimaging Multimodal bioimaging Lanthanides Inorganic chemistry |
| work_keys_str_mv | AT yuand responsivelanthanidedopednanoparticlesforbioimaging |