Ferritin is a spherical metalloprotein, capable of storing and releasing iron in a controllable way. It is composed of a protein shell of about 12 nm and within its cavity, iron is stored in a... Show moreFerritin is a spherical metalloprotein, capable of storing and releasing iron in a controllable way. It is composed of a protein shell of about 12 nm and within its cavity, iron is stored in a mineral form. The ferritin core resembles an iron-based nanoparticle that is isolated from the environment by the ferritin shell, which makes ferritin an attractive element to be used in the fabrication of bioelectronic devices. Another intriguing aspect of ferritin is its potential relation to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. The relation is not yet well understood, but the studies indicate that dysfunctional ferritin appears to play an important role. This dissertation aims to characterize ferritin electrically and magnetically. First, the electrical properties of single ferritin are explored to understand the charge transport through ferritin, and additionally, the first ferritin single-electron transistor is obtained. Second, the magnetic properties of multiple ferritin particles are studied by electron paramagnetic resonance, which supplies information about the ferritin core. A model of the electron-spin structure of the ferritin core is proposed and extended to the ferritin signal from post-mortem brain tissues. Show less
The findings in this thesis improve the understanding of 1) the relationship between exposure characteristics and toxicity of ENPs, 2) the joint toxic action of ENP mixtures and the comparison to... Show moreThe findings in this thesis improve the understanding of 1) the relationship between exposure characteristics and toxicity of ENPs, 2) the joint toxic action of ENP mixtures and the comparison to metal salt mixtures, 3) how NOM affects the individual and joint toxicity of ENPs, 4) the extent of trophic transfer of ENPs along aquatic food chains, 5) the influence factors on trophic transfer, and 6) bioaccumulation, distribution and toxic effect on predators. This knowledge would provide a basis for data on individual and joint toxicity, bioaccumulation, and trophic transfer of ENPs for more realistic environmental risk assessment. Show less
In this thesis, the researcher developed a nanosystem based on the metallophilic Interaction between cyclometalated complexes. Using this strategy, the researcher achieved efficient photodynamic... Show moreIn this thesis, the researcher developed a nanosystem based on the metallophilic Interaction between cyclometalated complexes. Using this strategy, the researcher achieved efficient photodynamic therapy to several cancers, accompanied by the cell imaging property. Show less
Copper nanoparticles (CuNPs) are used extensively in a wide range of products and the potential for toxicological impacts in the aquatic environment is of high concern. In this study, the fate and... Show moreCopper nanoparticles (CuNPs) are used extensively in a wide range of products and the potential for toxicological impacts in the aquatic environment is of high concern. In this study, the fate and the acute toxicity of spherical 50 nm copper nanoparticles was assessed in juvenile rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas) and zebrafish (Danio rerio) for in vivo aqueous exposures following standardized OECD 203 guideline tests. The fate of the CuNPs in the aqueous media was temperature dependent. At the higher study temperature (26 ± 1 C), there was both an enhanced particle aggregation and higher rate of dissolution compared with that at the lower study temperature (15 ± 1 C). 96 h LC50s of the CuNPs were 0.68 ± 0.15, 0.28 ± 0.04 and 0.22 ± 0.08 mg Cu/L for rainbow trout, fathead minnow and zebrafish, respectively. The 96 h lowest-observed-effect concentration (LOEC) for the CuNPs were 0.17, 0.023 and <0.023 mg/L for rainbow trout, fathead minnow, and zebrafish respectively, and are below the predicted environmental concentration of CuNPs for some aquatic environments suggesting a possible ecotoxicological risk to fish. Soluble copper was one of main drivers for the acute toxicity of the copper nanoparticles suspensions. Both CuNPs suspension and copper nitrate caused damage to gill filaments and gill pavement cells, with differences in sensitivity for these effects between the fish species studied. We show therefore common toxicological effects of CuNPs in different fish species but with differences in sensitivity with implications for hazard extrapolation between fish species. Show less
This thesis describes the use of MRI contrast agents and vessel wall parameters to image different stages of atherosclerosis. Chapter 2 summerizes different MRI contrast agents targeted towards... Show moreThis thesis describes the use of MRI contrast agents and vessel wall parameters to image different stages of atherosclerosis. Chapter 2 summerizes different MRI contrast agents targeted towards vulnerable plaques that have been presented in literature. Chapter 3 illustrates accumulation of paramagnetic micelles and liposomes in atherosclerosis, yet have complex kinetics when followed over time. In chapter 4 the use of self-gated MRI was validated to detect contrast agent accumulation in atherosclerotic plaques and assess the vessel wall compliance. The potential of both techniques to monitor plaque progression and anti-atherosclerotic therapy was assessed. In chapter 5 we developed a scavenger receptor-A1 targeted USPIO to detect vulnerable lesions. Chapter 6 describes the application of VCAM-1 targeted USPIO. Imaging at different time points, allows to discriminate early plaques from advanced lesions and can be used to monitor treatment response in ApoE-/- mice. In Chapter 7 an E-selectin targeted USPIO was validated. This USPIO allowed discrimination of lesions rich in macrophages from early lesions. In Chapter 8 we developed a micelle encapsulating rosiglitazone. Targeted delivery to the plaque lead to an anti-atheroscle rotic response without cardiac side-effects. Finally in Chapter 9 the potentials and pitfalls of histological validation of MRI contrast agents are illustrated. Show less
The work described in this thesis was aimed at the study of the functional properties of (isolated and purified) biomolecular systems at the single-molecule level. Two prerequisites are essential... Show moreThe work described in this thesis was aimed at the study of the functional properties of (isolated and purified) biomolecular systems at the single-molecule level. Two prerequisites are essential for successfully achieving this goal. First of all, single biomolecules should be observable, which means that they should be natively fluorescent or they should be rendered fluorescent by suitable biochemical or biomolecular 12 engineering. The other challenge is to engineer the system in such a way that the fluorescence intensity reports the actual, functional state of the biomolecule. Show less
