Titel: Labelling of cells with different materials for X-ray fluorescence imaging and cell targeting studies
Sprache: Englisch
Autor*in: Kang, Yanan
Erscheinungsdatum: 2022
Tag der mündlichen Prüfung: 2022-02-11
Zusammenfassung: 
X-ray imaging is a mature means of tissue imaging, making iodine-based contrast agents widely used in various scientific research and clinical imaging. After more than half a century of development, commercial iodine-containing contrast agents have been characterized by high water solubility, low biobinding, low toxicity, and high biotolerance. However, due to their rapid renal excretion and high dosage, they still damage the function of kidneys, heart, and thyroid. In order to find an optimal way of iodine delivery, small iodine-containing molecules (4IH) were labeled on BSA, dextran, PMA coated AuNPs, and synthesized iodine-doped AgI NPs, commercial contrast agent iohexol as the control. ICP-MS detected the content of iodine in each carrier, and the labeling efficiency was: PMA-Au-I
PSMA small molecule inhibitors have the advantages of good cell permeability and fast blood clearance, making them the first choice for constructing PCa molecular probes. Most of the small molecule reagents prepared for PSMA imaging and treatment are based on urea scaffolds. The glutamate-urea-based motif is a highly appropriate building block for preparing effective PSMA inhibitors. At present, research hotspots at home and abroad are mainly focused on developing nuclide-labeled molecules with a high affinity to PSMA. There are few studies on nanoparticles that use PSMA small molecule inhibitors as targets. Here, we prepared PSMA targeting nanoparticles with a small sulfhydryl ligand, mercaptoundecanoic acid (MUA) as a spacer, and a glutamate-urea-based PSMA small molecule inhibitor a targeting molecule. In vitro stability studies and cell uptake experiments showed that small MUA functional ligand could not maintain sufficient stability of AuNP in cell culture medium, and the aggregation of nanoparticles resulted in no obvious evidence of the targeting of PSMA-I, which required further optimization of the ligand before investigation.

With the in-depth study of targeted nanoparticles, researchers have found that the targeting efficiency of nanoparticles is deeply affected by factors such as the antibody density or size or direction on the surface. However, the platform to investigate the targeting efficiency of a single variable is still missing. It is not easy to find conclusive evidence that their surface antibody density determines the targeting efficiency of nanoparticles. To this end, we used scFv and SNAP-tag to control the effect of antibody size and orientation and constructed a platform to investigate the impact of antibody density on targeting efficiency with a single variable. The successful preparation and purification of AuNPs with a discrete number of ligands highlights their potential as a reliable platform for studying the relationship between targeting efficiency and antibody density.
URL: https://ediss.sub.uni-hamburg.de/handle/ediss/9478
URN: urn:nbn:de:gbv:18-ediss-98900
Dokumenttyp: Dissertation
Betreuer*in: Parak, Wolfgang
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen

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Yanan Kang _Doctoral thesis_print.pdfYanan Kang_Dissertation2eb68aeccd0258f6363778a5821ce5df5.73 MBAdobe PDFÖffnen/Anzeigen
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