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  • 1.
    Eriksson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Cerium Oxide Nanoparticles and Gadolinium Integration: Synthesis, Characterization and Biomedical Applications2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    A challenging task, in the area of magnetic resonance imaging is to develop contrast enhancers with built-in antioxidant properties. Oxidative stress is considered to be involved in the onset and progression of several serious conditions such as Alzheimer’s and Parkinson’s disease, and the possibility to use cerium-contained nanoparticles to modulate such inflammatory response has gained a lot of interest lately. The rare earth element gadolinium is, due to its seven unpaired f-electrons and high symmetry of the electronic state, a powerful element for contrast enhancement in magnetic resonance imaging. Chelates based on gadolinium are the most commonly used contrast agents worldwide. When introducing external contrast agents there is always a risk that it may trigger inflammatory responses, why there is an urgent need for new, tailor-made contrast agents.

    Small sized cerium oxide nanoparticles have electronic structures that allows coexistence of oxidation states 3+ and 4+ of cerium, which correlates to applicable redox reactions in biomedicine. Such cerium oxide nanoparticles have recently shown to exhibit antioxidant properties both in vitro and in vivo, via the mechanisms involving enzyme mimicking activity.

    This PhD project is a comprehensive investigation of cerium oxide nanoparticles as scaffold materials for gadolinium integration. Gadolinium is well adopted into the crystal structure of cerium oxide, enabling the combination of diagnostic and therapeutic properties into a single nanoparticle. The main focus of this thesis project is to design cerium oxide nanoparticles with gadolinium integration. A stepwise approach was employed as follows: 1) synthesis with controlled integration of gadolinium, 2) material characterization by means of composition crystal structure, size, and size distribution and 3) surface modification for stabilization. The obtained nanoparticles exhibit remarkable antioxidant capability in vitro and in vivo. They deliver strongly enhanced contrast per gadolinium in magnetic resonance imaging, compared to commercially available contrast agents.

    A soft shell of dextran is introduced to encapsulate the cerium oxide nanoparticles with integrated gadolinium, which protects and stabilizes the hard core and to increases their biocompatibility. The dextran-coating is clearly shown to reduce formation of a protein corona and it improves the dispersibility of the nanoparticles in cell media. Functionalization strategies are currently being studied to endow these nanoparticles with specific tags for targeting purposes. This will enable guidance of the nanoparticles to a specific tissue, for high local magnetic resonance contrast complemented with properties for on-site reduced inflammation.

    In conclusion, our cerium oxide nanoparticles with integrated gadolinium, exhibit combined therapeutic and diagnostic, i.e. theragnostic capabilities. This type of nanomaterial is highly promising for applications in the field of biomedical imaging.

    Delarbeid
    1. Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement
    Åpne denne publikasjonen i ny fane eller vindu >>Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement
    Vise andre…
    2018 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 6999Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue-and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3-5 nm in size, have r(1)-relaxivities between 7-13 mM(-1) s(-1) and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

    sted, utgiver, år, opplag, sider
    Nature Publishing Group, 2018
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-147910 (URN)10.1038/s41598-018-25390-z (DOI)000431293100003 ()29725117 (PubMedID)2-s2.0-85046679522 (Scopus ID)
    Merknad

    Funding Agencies|Swedish Research Council [621-2013-5357]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]; Knut and Alice Wallenberg Foundation [2012.0083 CTS 15:507]; Centre in Nano Science and Nano technology at LiTH (CeNano) at Linkoping University; CoTXS; Ministry of Education and Science of the Russian Federation [14.Y26.31.0005, K2-2017-080, 211]

    Tilgjengelig fra: 2018-05-23 Laget: 2018-05-23 Sist oppdatert: 2019-08-29bibliografisk kontrollert
  • 2.
    Eriksson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Tal, Alexey
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Fysik. Linköpings universitet, Tekniska fakulteten.
    Skallberg, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Brommesson, Caroline
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Hu, Zhang-Jun
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Boyd, Robert
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Plasma och beläggningsfysik. Linköpings universitet, Tekniska fakulteten.
    Olovsson, Weine
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Fysik. Linköpings universitet, Tekniska fakulteten.
    Fairley, Neal
    Casa Software Ltd, Bay House, Teignmouth, United Kingdom.
    Abrikosov, Igor
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teoretisk Fysik. Linköpings universitet, Tekniska fakulteten. Materials Modeling and Development Laboratory, National University of Science and Technology “MISIS”, Moscow, Russia.
    Zhang, Xuanjun
    Faculty of Health Sciences, University of Macau, Macau, SAR, China.
    Uvdal, Kajsa
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 6999Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue-and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3-5 nm in size, have r(1)-relaxivities between 7-13 mM(-1) s(-1) and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

  • 3.
    Hu, Zhang-Jun
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Yang, Guanqing
    Anhui Univ, Peoples R China.
    Hu, Jiwen
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Wang, Hui
    Anhui Univ, Peoples R China.
    Eriksson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Zhang, Ruilong
    Anhui Univ, Peoples R China.
    Zhang, Zhongping
    Anhui Univ, Peoples R China.
    Uvdal, Kajsa
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
    Real-time visualizing the regulation of reactive oxygen species on Zn2+ release in cellular lysosome by a specific fluorescent probe2018Inngår i: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 264, s. 419-425Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reactive oxygen species (ROS) regulating the release of free zinc ions (Zn2+) in cellular lysosome is closely related to various pathways of cellular signal transduction, such as inflammation and oxidative stress. Directly visualizing Zn2+ release in lysosome is essential for in-depth understanding these physiological processes, and is still an atelic challenge. In this work, we successfully fabricate a lysosome-specific Zn2+ fluorescent probe and achieve the visualization of ROS-induced Zn2+ release in lysosome of inflammatory cells. The as-prepared probe combines a green fluorophore, an ionophore with five-dentate sites, and a morpholine as the lysosome-specific localization moiety. The fluorescence of the fluorophore in the free probe is suppressed by a photoinduced electron transfer (PET) process from nitrogen atoms in the ionophore. Upon the addition of Zn2+, the fluorescence can be promoted immediately, achieving the real-time detection. Meanwhile, the probe is sensitive and selective to Zn2+, which provides the capability to detect low-concentration of free Zn2+ in lysosomes. Accordingly, the Zn2+ release was clearly observed in lysosome with the increase of ROS levels when the inflammation occurred in living cells. (c) 2018 Published by Elsevier B.V.

    Fulltekst tilgjengelig fra 2020-03-07 12:11
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