Is the PEGylation of indium phosphide/zinc sulphide quantum dots the first step in creating a platelet biocompatible multimodal imaging agent?

Booth, Zoe

Abstract

Background:
Indium phosphide/zinc sulphide (InP/ZnS) quantum dots (QDs) are semiconductive nanoparticles that have received growing focus due to the perception that they are safer than heavy metal based QDs. InP/ZnS QDs possess a highly fluorescent and tuneable emission, whilst seemingly being less toxic compared to other commonly used cadmium based QDs. Furthermore, the QDs can be conjugated to allow them to be imaged by MRI. These properties make the QDs potentially useful for biological based imaging techniques, specifically those concerned with platelets. Platelets can be sensitive to environmental changes, therefore controlling the QD reactivity by tailoring QD synthesis and coating, including the use of ‘stealth’ agents is crucial to minimising platelet reactivity, and thereby improving biocompatibility. Therefore, the aim of this thesis is to determine if a viable InP/ZnS based multimodal imaging agent, with minimal effects on platelets could be developed.
Methods used:
The InP/ZnS QDs were produced in-house. During QD synthesis, different core precursors (InCl₃, InI₃, InBr₃) and ligand coatings (lipoic acid, glutathione, thioglycolic acid and penicillamine) were produced. From there, certain QDs were PEGylated and then gadolinium was conjugated. These different QD types were incubated with healthy human washed platelets before numerous functionality tests were carried out to determine if the QDs interfered with platelet aggregation, spreading, and platelet activation monitored via flow cytometry. Additionally, in vitro flow assays using collagen coated microfluidic chips were used to determine if the QDs incubated in whole blood affected thrombus formation.
Results obtained:
Utilising the InCl3 core precursor and coating the QDs with either penicillamine or thioglycolic acid ligands was shown to affect platelet functionality the least. PEGylation was also crucial in further reducing the observed reactivity of the QDs with platelets, as identified in platelet aggregation, spreading, flow cytometry and under shear and static conditions. A multimodal QD was developed by conjugating gadolinium to InP/ZnS QDs. This QD showed minimal platelet reactivity, but only in cases where it had been PEGylated first. The most viable example of this was the PEGylated, gadolinium coated, penicillamine QD (R.QD-pen-PEG-Gd), as no significant effect on platelet functionality was observed, even at concentrations up to 100 nM.
Conclusions made:
Overall, these findings provide the first insight not only into how InP/ZnS QDs can be engineered to be more platelet biocompatible, but also the specific concentrations that do not induce any change in platelet functionality. Therefore, future work could focus on the addition of a platelet specific antibody. From there, a platelet-based multimodal imaging agent could be developed, applicable in studying the role of platelets not only in cardiovascular diseases, but also in wider biological processes within the body.

Citation

Booth, Z. Is the PEGylation of indium phosphide/zinc sulphide quantum dots the first step in creating a platelet biocompatible multimodal imaging agent?. (Thesis). Hull York Medical School. https://hull-repository.worktribe.com/output/4790560

• Thesis Type: Thesis
• Deposit Date: Aug 22, 2024
• Keywords: Medical sciences
• Public URL: https://hull-repository.worktribe.com/output/4790560
• Additional Information: Hull York Medical School; University of Hull and University of York
• Award Date: Jan 1, 2024