Thesis
Investigation of the detection and quantification of nanomaterials in biomatrices for cancer research applications
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2023
- Thesis identifier
- T16744
- Person Identifier (Local)
- 201955925
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Cancer constitutes a global health issue and the leading cause of death worldwide, therefore scientific research has shifted towards advancing conventional methods for cancer screening, diagnostics, and therapeutics. Surface enhanced Raman scattering (SERS) is a valuable optical imaging tool for cancer research, as it offers a non-destructive platform for molecular targeting that due to its non-destructive nature can be used alongside complementary imaging techniques. The overarching aim of this research was to explore the potential of a multi-modal imaging platform consisting of SERS and laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-ToF-MS) imaging. The dual-imaging modality was used for the detection and quantification of nanomaterials in biomatrices, such as cells and tissues, to demonstrate the advantages of nanotechnology in cancer research applications. A quantification model for SERS was developed, correlating the SERS signals obtained to the elemental information of the nanotags. Bioprinting was used to produce gelatin calibration standards whose suitability for quantification was demonstrated by LA-ICP-ToF-MS. This work provided an important advancement towards absolute SERS quantitation that remains a challenge within the SERS community. Investigation of the impact of using nanoparticle conjugates to improve the targeted drug delivery capability of the antitumoral drug cisplatin was also undertaken. This work demonstrated the feasibility of using SERS and LA-ICP-ToFMS imaging for tracking intracellular uptake of cisplatin conjugates, where the location of both drug and nanoparticles can be ascertained as individual species, in cell models. This opens avenues for exploring the quantification of intracellular drug concentration. Additional investigation of the conjugate’s mode of action demonstrated their effectiveness in inducing cytotoxicity and delivering Pt intracellularly. Finally, the detection of nanomaterials through tissue was investigated. The superior depth penetration capabilities offered by SESORS compared to SERS were demonstrated for alkyne-tagged nanoprobes, expanding the SORS detection capabilities in the biologically silent spectral region. This thesis highlights the capabilities of SERS underpinned by MS techniques for the detection and quantification of nanomaterials in biological matrices. The wide range of information obtained at a single-cell level improve better understanding of the biological processes relating to cancer and demonstrate the advantages of nanotechnology in cancer research.
- Advisor / supervisor
- Faulds, Karen
- Graham, Duncan
- Goenaga-Infante, Heidi
- Resource Type
- DOI
- Embargo Note
Relations
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File | 2023-10-24 | Embargo |