Development of Multimodal Imaging Agents for Thrombosis

Gil, Helio

Abstract

Quantum dots (QDs) are colloidal nanoparticles with unique optical and electronic characteristics attributed to quantum confinement effects, making them ideal for fluorescence imaging of biological systems. This thesis investigates the synthesis and characterization of various QDs systems, exploring the characterisation of their fluorescent properties, surface chemistry and their effects on the blood cell the platelet.
InP/ZnS QDs were synthesized using a hot-injection method, revealing concentration-dependent self-quenching or energy transfer effects at concentrations above 1 μM. The same effect was verified for QDs phase transferred with different surface ligands (thioglycolic acid, penicillamine, lipoic acid and glutathione). Platelet studies helped define surface coatings (thioglycolic acid and penicillamine) and concentrations of QDs that are compatible with platelet function (up to 100 nM), while demonstrating localisation of QDs on the surface of the platelets.
The synthesis of dual modal magnetic resonance/fluorescent imaging agents was explored. Bifunctional chelators based on DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid) were synthesized to complex lanthanide ions, producing DOTAGA-LA-EDA complexed, which was grafted onto the surface of InP/ZnS QDs, forming a multimodal probe. This probe retained the fluorescent properties of isolated QDs, and relaxivity studies confirmed its magnetic properties (r1 = 5.70 mM-1.s-1 at 400 MHz). A QD delivery system based on liposomes was also developed, achieving sizes of 68.3 ± 1.8 nm and up to 86% encapsulation efficiency using a microfluidic approach. This encapsulation also pointed towards higher compatibility with platelets, as verified by aggregation and spreading assays.
A different material for QDs, which emitted closer to the NIR range and used a faster, more reproducible methodology, was also explored. CuInS2/ZnS QDs in water were synthesized via a microwave method, achieving near-infrared emission peaks at 705 nm by optimizing reaction parameters such as temperature, time, pH and Cu ratio. Temperatures of 110 ºC and longer core growth times favoured the formation of redshifted QDs. Acidic pH (5) also led to the formation of redshifted QDs (865 nm) but with compromised stability. Cu:In ratios considerably influenced emission, with a redshift from 585 to 705 nm as the ratio changed from 1:8 to 1:2, the latter being optimal for achieving the desired emission peak.
This work provides valuable insights into the development of QDs as multimodal probes for biomedical imaging. Optical studies address concentration-related effects of QDs, and combined with platelet studies, enhance the understanding of their biocompatibility. Additionally, the creation of an efficient liposome-based QD delivery system paves the way for advanced in vivo imaging techniques, particularly in the context of platelet imaging and other biological
applications.

Citation

Gil, H. (2025). Development of Multimodal Imaging Agents for Thrombosis. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/5088352

• Thesis Type: Thesis
• Deposit Date: Mar 25, 2025
• Publicly Available Date: Jan 23, 2030
• Keywords: Biomedical sciences
• Public URL: https://hull-repository.worktribe.com/output/5088352
• Additional Information: Biomedical Sciences; Faculty of Health Sciences; University of Hull
• Award Date: Jan 22, 2025