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Superparamagnetic nanoparticles loaded in red blood cells as novel contrast agents for in vivo diagnostic techniques in the biomedical field.
No full textNanomedicine has revolutionized biomedical research by integrating diagnostic and therapeutic functionalities into novel platforms. This thesis explores the engineering of red blood cells (RBCs) as biocompatible carriers for superparamagnetic iron oxide nanoparticles (SPIONs), offering a groundbreaking approach for in vivo imaging and drug delivery applications. RBCs provide a unique advantage due to their long circulatory lifespan, immune evasion properties, and capability to encapsulate various nanomaterials, thereby enhancing the stability and efficiency of contrast agents used in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI).
The research focuses on optimizing the synthesis of SPIONs through a multi-step process, incorporating advanced surface coating techniques with citrate and dextran to improve monodispersity, stability, and encapsulation efficiency. The encapsulation of SPIONs into RBCs was achieved by transiently opening membrane pores via reversible hypotonic hemolysis, ensuring nanoparticle internalization while maintaining cell viability. Among the synthesized nanoparticles, formulations such as MNPs 29DX-filt 0.1 and MNPs 40 DX-filt 0.1 demonstrated superior performance in both human and murine RBCs.
Comprehensive characterization techniques, including Transmission Electron Microscopy (TEM), Nuclear Magnetic Resonance (NMR), Magnetic Particle Spectroscopy (MPS), and preclinical MRI at 1 Tesla, were employed to assess the physicochemical properties and imaging potential of these constructs. Notably, MPS, an emerging technology linked to MPI, revealed enhanced tracer quantification capabilities, reinforcing the suitability of SPION-loaded RBCs for high-sensitivity imaging applications.
This work also investigates the potential of RBC-encapsulated SPIONs as an alternative to conventional blood oxygenation level-dependent (BOLD) contrast agents for functional MRI (fMRI). The use of Ferucarbotran®-loaded RBCs (FLH-RBCs) for cerebral blood volume (CBV)-weighted fMRI demonstrates improved spatial specificity and prolonged circulation compared to free SPIONs, offering a transformative approach for functional brain mapping. Preclinical studies in rodent models validated the efficacy of this novel imaging strategy, showing superior cortical layer resolution over traditional BOLD-based techniques.
Furthermore, a key aspect of this research is the integration of automation trials in the RBC-loading process, conducted in collaboration with EryDel S.p.A. The development of an automated system for Ferucarbotran® encapsulation could ensure reproducibility, scalability, and clinical feasibility, overcoming challenges associated with manual loading methods.
Beyond imaging, the thesis explores the compatibility of nucleobase-containing platinum(II) complexes with RBCs for potential anticancer and antiviral drug delivery. Encapsulation studies demonstrated that RBCs effectively protect these therapeutic agents from rapid degradation, ensuring controlled release and improved biodistribution. The feasibility of loading various metal-based nucleoside derivatives into RBCs opens new avenues for advanced targeted therapies.
Overall, this work highlights the remarkable versatility of RBC-encapsulated nanomaterials for biomedical applications, offering innovative solutions for molecular imaging, targeted drug delivery, and functional neuroimaging. By leveraging the unique biophysical properties of RBCs and state-of-the-art nanotechnology, this research paves the way for the development of next-generation diagnostic and therapeutic strategies.Nanomedicine has revolutionized biomedical research by integrating diagnostic and therapeutic functionalities into novel platforms. This thesis explores the engineering of red blood cells (RBCs) as biocompatible carriers for superparamagnetic iron oxide nanoparticles (SPIONs), offering a groundbreaking approach for in vivo imaging and drug delivery applications. RBCs provide a unique advantage due to their long circulatory lifespan, immune evasion properties, and capability to encapsulate various nanomaterials, thereby enhancing the stability and efficiency of contrast agents used in magnetic resonance imaging (MRI) and magnetic particle imaging (MPI).
The research focuses on optimizing the synthesis of SPIONs through a multi-step process, incorporating advanced surface coating techniques with citrate and dextran to improve monodispersity, stability, and encapsulation efficiency. The encapsulation of SPIONs into RBCs was achieved by transiently opening membrane pores via reversible hypotonic hemolysis, ensuring nanoparticle internalization while maintaining cell viability. Among the synthesized nanoparticles, formulations such as MNPs 29DX-filt 0.1 and MNPs 40 DX-filt 0.1 demonstrated superior performance in both human and murine RBCs.
Comprehensive characterization techniques, including Transmission Electron Microscopy (TEM), Nuclear Magnetic Resonance (NMR), Magnetic Particle Spectroscopy (MPS), and preclinical MRI at 1 Tesla, were employed to assess the physicochemical properties and imaging potential of these constructs. Notably, MPS, an emerging technology linked to MPI, revealed enhanced tracer quantification capabilities, reinforcing the suitability of SPION-loaded RBCs for high-sensitivity imaging applications.
This work also investigates the potential of RBC-encapsulated SPIONs as an alternative to conventional blood oxygenation level-dependent (BOLD) contrast agents for functional MRI (fMRI). The use of Ferucarbotran®-loaded RBCs (FLH-RBCs) for cerebral blood volume (CBV)-weighted fMRI demonstrates improved spatial specificity and prolonged circulation compared to free SPIONs, offering a transformative approach for functional brain mapping. Preclinical studies in rodent models validated the efficacy of this novel imaging strategy, showing superior cortical layer resolution over traditional BOLD-based techniques.
Furthermore, a key aspect of this research is the integration of automation trials in the RBC-loading process, conducted in collaboration with EryDel S.p.A. The development of an automated system for Ferucarbotran® encapsulation could ensure reproducibility, scalability, and clinical feasibility, overcoming challenges associated with manual loading methods.
Beyond imaging, the thesis explores the compatibility of nucleobase-containing platinum(II) complexes with RBCs for potential anticancer and antiviral drug delivery. Encapsulation studies demonstrated that RBCs effectively protect these therapeutic agents from rapid degradation, ensuring controlled release and improved biodistribution. The feasibility of loading various metal-based nucleoside derivatives into RBCs opens new avenues for advanced targeted therapies.
Overall, this work highlights the remarkable versatility of RBC-encapsulated nanomaterials for biomedical applications, offering innovative solutions for molecular imaging, targeted drug delivery, and functional neuroimaging. By leveraging the unique biophysical properties of RBCs and state-of-the-art nanotechnology, this research paves the way for the development of next-generation diagnostic and therapeutic strategies
Encapsulation in human and murine erythrocytes of the Synomag®-D-PEG-OMe tracer for MPI application
No full textRecently, the potential of red blood cells (RBCs) loaded with superparamagnetic iron oxide (SPIO)-based nanoparticles as new blood-pool tracer material for the Magnetic Particle Imaging (MPI) has been investigated. It was shown
that the encapsulation of SPIO-based contrast agents in the RBCs increase the circulation time in blood of these
nanomaterials. However, not all iron oxide nanoparticles are eligible to the encapsulation into RBCs, depending
on several factors such as dispersant agent nature, nanoparticle size and synthesis protocol. Therefore, we have
recently started a program to identify those nanoparticles that can be potentially loaded with our method into RBCs.
The goal is to produce biocompatible SPIO-RBCs carriers that can be used as new intravascular magnetic susceptible
agents in biomedical applications, such as MRI and MPI. Here, we report the in vitro results obtained by using
the Synomag®-D-PEG-OMe nanoparticle suspension (micromod Partikeltechnologie GmbH) with both human
and murine red blood cells. MPS analysis showed that human Synomag®-D-PEG-OMe-loaded RBCs produced a
signal that is weaker respect to the remarkable signal of ferucarbotran loaded-RBCs prepared at the same condition,
but it is to be noted that the encapsulation efficiency of Synomag®-D-PEG-OMe into cells is lower compared to
ferucarbotran nanoparticles
Optimization of magnetic nanoparticles for engineering erythrocytes as theranostic agents
Get PDFThe application of superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery, magnetic resonance imaging, cell tracking, and hyperthermia has been long exploited regarding their inducible magnetic properties. Nevertheless, SPIONs remain rapidly cleared from the circulation by the reticuloendothelial system (RES) or mononuclear phagocyte system, with uptake dependent on several factors such as the hydrodynamic diameter, electrical charge and surface coating. This rapid clearance of SPION-based theranostic agents from circulation is one of the main challenges hampering the medical applications that differ from RES targeting. This work proposes a strategy to render biocompatible SPIONs through their encapsulation in the red blood cells (RBCs). In this work, the research has been focused on the multi-step optimization of chemical synthesis of magnetic nanoparticles (MNPs), precisely iron oxide nanoparticles (IONPs) and zinc manganese-ferrite nanoparticles (Zn/Mn FNPs), for encapsulation in human and murine RBCs. The encapsulation through the transient opening of RBC membrane pores requires extensive efforts to deliver high-quality nanoparticles in terms of chemical properties, morphology, stability and biocompatibility. After reaching this goal, in vitro experiments were performed with selected nanomaterials to investigate the potential of engineered MNP-RBC constructs in theranostic approaches
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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