Author: | Fung, Yuen On Dorothy |
Title: | Luminescent lanthanide metal complexes in biomedical imaging |
Degree: | Ph.D. |
Year: | 2013 |
Subject: | Complex compounds. Imaging systems in biology. Imaging systems in medicine. Hong Kong Polytechnic University -- Dissertations |
Department: | Department of Applied Biology and Chemical Technology |
Pages: | 179 leaves : ill. (some col.) ; 30 cm. |
Language: | English |
Abstract: | Cyclen-based macrocyclic lanthanide(III) complexes have been found to have extremely high thermodynamic and kinetic stability. DO3A (1,4,7,10-tetraazacyclodecane-1,4,7-triacetate) is used as template for developing lanthanides complexes for molecular imaging, medical diagnosis or therapy. They showed excellent water solubility and stability in-vitro/in-vivo. Like monomeric DO3A complexes, dimeric DO3A complexes have the potential of being used as ultrasensitive bioassays and Gd complexes as magnetic resonance imaging (MRI) contrast agents. A general background and the coordination chemistry of lanthanide, their characteristic luminescent properties and their applications in biological systems were reviewed. A series of dimeric and monomeric DO3A lanthanide complexes (LnL1- LnL4, Ln = Gd, Eu and Tb) were synthesized and bridging with two different triazine chromophores (phenyl-1,3,5-triazine and N,N-diethyl-4-(1,3,5-triazin-2-yl)benzenamine). Photophysical measurements such as f-f emission, life time, q-value and f-f emission quantum yield, were carried out in order to study and understand the properties of the complexes. Both monomeric and dimeric complexes have a maximum excitation at around 300 nm. The luminescence properties have been thoroughly studied and the changes in photophysical properties and the sensitivity towards some endogenous anions are rationalized. In general, studies indicated that the chromophore, phenyl-1,3,5-triazine, in EuL₁ and EuL₂ give higher efficiency than that in EuL₃ and EuL₄. Another two dimeric DO3A lanthanide complexes (LnL₅ - LnL₆, Ln = Gd, Eu and Tb) were synthesized with two different amide bridging chromophores respectively. Photophysical measurements indicated that the bridged with bisphenyl antenna in LnL₆ gives a higher efficiency than that in LnL₅ with adequate f-f emission quantum yield of 7 %. EuL₆ is responsive to the protein, Human Serium Ablum (HSA) giving an f-f- luminescence signal enhancement with binding constant (logK = 4.84). The positive protein affinities of EuL₆ and HSA have been performed by gel electrophoresis. Also, the stability of these two lanthanide complexes were examined with the tritration of various biological molecules, such as citrate and urate. In-vitro imaging of EuL₅ and EuL₆ in HeLa cells were recorded and EuL₆ demonstrated a higher rate of cellular uptake and low cytotoxicity (IC₅₀ = 3 mM). |
Rights: | All rights reserved |
Access: | open access |
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