Novel Polymeric Magnetic Resonance Imaging (MRI) Contrast Agents PDF Download

Author: Steven MacLellan
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Author: Jonathan Martinelli
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Author: Sophie Laurent
Publisher: Springer
ISBN: 9811025290
Category : Technology & Engineering
Languages : en
Pages : 128

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This book describes the multiple aspects of (i) preparation of the magnetic core, (ii) the stabilization with different coatings, (iii) the physico-chemical characterization and (iv) the vectorization to obtain specific nanosystems. Several bio-applications are also presented in this book. In the early days of Magnetic Resonance Imaging (MRI), paramagnetic ions were proposed as contrast agents to enhance the diagnostic quality of MR images. Since then, academic and industrial efforts have been devoted to the development of new and more efficient molecular, supramolecular and nanoparticular systems. Old concepts and theories, like paramagnetic relaxation, were revisited and exploited, leading to new scientific tracks. With their high relaxivity payload, the superparamagnetic nanoparticles are very appealing in the context of molecular imaging but challenges are still numerous: absence of toxicity, specificity, ability to cross the biological barriers, etc.

Author: Clare Lee Matilda Le Guyader
Publisher:
ISBN:
Category :
Languages : en
Pages : 228

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Nanoparticles are the hallmark of nanomedicine, proving clinically relevant for the delivery of therapeutic and diagnostic drugs. Nanomaterials are highly versatile, with the ability for scientists to tailor composition and function to suit the desired application. Herein, two types of nanocarriers are investigated in the context of magnetic resonance imaging contrast agents: polymeric nanoparticles and protein carriers. A key research focus in applying nanoparticles for drug delivery is in understanding physicochemical properties affecting in vivo fate. Shape or morphology of a particle is a vastly underutilized property in the design of nanoparticles, and is difficult to predictably control in the context of polymeric nanoparticles. Investigations of block copolymer nanoassemblies evaluate effects of the polymer structure and the self-assembly process to form interesting and diverse structures. In this work, ring-opening metathesis polymerization is employed to prepare and study block copolymer amphiphile self-assembly. First, a small library of amphiphiles are prepared in which the hydrophobic block functionality is varied. In varying the polymer structure and the solvent for assembly, different morphologies are produced, including small and large spheres, cylinders, y-junctions, and rods. In several cases, one polymer can take on different morphologies depending on the organic cosolvent used during micellization, highlighting the importance of assembly conditions and dynamics in forming kinetically trapped structures versus thermodynamically stable structures. These are important considerations when designing, synthesizing, and formulating polymeric nanoparticles for in vivo applications. Next, direct incorporation of a gadolinium based contrast agent for magnetic resonance imaging is studied. A novel monomer and chain transfer agent of a gadolinium-chelate are used to directly incorporate the contrast agent in to a polynorbornene polymer backbone. The resulting spherical and fibrillar nanoparticles exhibited enhanced relaxivity and are studied as MRI contrast agents using live imaging in murine models. Finally, a fatty acid ligand is conjugated to a gadolinium-based contrast agent is prepared and formulated with human serum albumin. In formulation with HSA, the agent exhibits high relaxivity and prolonged blood circulation. In addition, therapeutic conjugates formulated with HSA are evaluated for in vitro cytotoxicity and found to be effective in tumor growth suppression in vivo.

Author: Jessica Rose McCombs
Publisher:
ISBN:
Category :
Languages : en
Pages : 49

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Macromolecular scaffolds for drug delivery, self-assembly, and imaging applications have attracted significant attention over the last several decades. As polymerization techniques become more sophisticated, it becomes possible to create polymeric architectures with increasing control over structure, molecular weight, and mass dispersity. Herein, ring-opening metathesis polymerization (ROMP) is paired with highly efficient synthetic methods to create functional bottle-brush polymers for MRI imaging and self-assembly applications. In this "graft-through" approach, bivalent macromonomers bearing a terminal exo-norbornene group were synthesized and polymerized to yield bottle-brush polymers with controlled molar masses and low dispersities. This approach is first utilized in the development of organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). These ORCAs are composed of macromonomers bearing long polyethylene glycol chains and sterically hindered bis(spirocyclohexyl) nitroxide free radicals. This approach enables facile tuning of nitroxide loading percentages and molecular size. Bottle-brush ORCAs displayed high r1 and r2 relaxivities suggesting that they have potential for further in vivo MRI studies. Next, bottle-brush copolymers composed of multiple polymeric domains are synthesized by ROMP. We propose that these multi-block bottle-brush polymers will self-assemble into interesting solution and bulk architectures. Several approaches to synthesizing tetrablock bottle-brush polymers were explored by combining "graft-through" and "graft-from" polymerization methods.

Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 12

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Author: Werner Krause
Publisher: Springer
ISBN: 354045733X
Category : Science
Languages : en
Pages : 251

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Extracellular MRI and X-ray contrast agents are characterized by their phar- cokinetic behaviour.After intravascular injection their plasma-level time curve is characeterized by two phases. The agents are rapidly distributed between plasma and interstitial spaces followed by renal elimination with a terminal half-live of approximatly 1–2 hours. They are excreted via the kidneys in unchanged form by glomerular filtration. Extracellular water-soluble contrast agents to be applied for X-ray imaging were introduced into clinical practice in 1923. Since that time they have proved to be most valuable tools in diagnostics.They contain iodine as the element of choice with a sufficiently high atomic weight difference to organic tissue. As positive contrast agents their attenuation of radiation is higher compared with the attenuation of the surrounding tissue. By this contrast enhancement X-ray diagnostics could be improved dramatically. In 2,4,6-triiodobenzoic acid derivatives iodine is firmly bound. Nowadays diamides of the 2,4,6-triiodo-5-acylamino-isophthalic acid like iopromide (Ultravist, Fig. 1) are used as non-ionic (neutral) X-ray contrast agents in most cases [1].

Author: Carlos Bárcena
Publisher:
ISBN:
Category : Magnetic materials
Languages : en
Pages : 216

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In recent years, magnetic nanoparticles have played an increasing role in biomedical applications and have been the subject of extensive research investigations. Physical properties, including nanoparticle size, composition and surface chemistry, vary widely and influence their biological and pharmacological properties and, ultimately, their clinical applications and utilities. Among different magnetic nanoparticles, superparamagnetic iron oxide nanoparticles (SPIOs) were found non-toxic and used in multiple applications including magnetic resonance imaging (MRI) contrast agents, molecular and cellular imaging, and potential therapeutic options. Herein, a mixed spinel strategy was devised to increase the magnetization of SPIO by incorporation of non-magnetic Zn 2+ . Addition of a normal spinel (ZnFe 2 O 4) to an inverse spinel (Fe 3 O 4) results in a magnetic disorder which leads to increased magnetization. Hydrophobic Zn x Fe 1-x O Fe 2 O 3 (x = 0.34) nanoparticles encapsulated in polymeric micelles exhibited increased T 2 relaxivity and sensitivity of detection over commercially used Feridex ® sample. The superb MR relaxivity of these Zn-SPIO nanoparticles and stability of micellar carriers make them excellent candidates for in vivo MR imaging of cancer.

Author: Hanlin Ou
Publisher: Frontiers Media SA
ISBN: 2832540937
Category : Science
Languages : en
Pages : 109

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Author: Liang Du
Publisher:
ISBN:
Category : Chemistry
Languages : en
Pages : 0

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The unique physical and optical properties of inorganic nanocrystals have generated tremendous interest over the past two decades. They have been extensively studied to prepare photovoltaic devices and diagnostic tools. Luminescent quantum dots, gold nanomaterials and iron oxide nanoparticles have found promising success in a broad range of areas including light-emitting diodes, therapeutic tomography, photodynamic therapy drug delivery and magnetic resonance imaging. However, most of the as-prepared nanoparticles are stabilized by hydrophobic coordinating ligands which impede their biological applications. In this dissertation, we summarize the application of poly(isobutylene-alt-maleic anhydride) (PIMA) polymer platform to prepare biocompatible nanomaterials as well as MRI contrast agents. In chapter 2, we designed a new set of multi-coordinating polymer ligands based on the phosphonate anchoring motif and applied them for the surface coating of luminescent quantum dots, gold nanoparticles and iron oxide nanoparticles alike. The ligand is synthesized via nucleophilic addition reaction between poly(isobutylene-alt-maleic anhydride) and amine-modified phosphonate derivatives and short polyethylene glycol hydrophilic blocks, which allows the flexibility to tune the architecture and stoichiometry of the final compound. We find that these phosphonate-based polymers exhibit strong coordinating affinity to ZnS-overcoated quantum dots (QDs), Au nanoparticles (AuNPs) as well as iron oxide nanoparticles (IONPs), yielding nanocrystal dispersions that exhibit good colloidal stability for all three systems. The affinity of these ligands is also preserved when additional coordinating groups are introduced, such as imidazoles. Furthermore, the resulting polymer-coated nanocrystals are easily functionalized with reactive groups, introduced along the polymer chain during synthesis. They are compact enough to allow implementation of resonance energy transfer coupling of luminescent QDs to proximal dyes. Affinity between the ligands and gold nanoparticle surfaces was compared to that of thiol groups using NaCN digestion tests. In Chapter 3, we designed a novel set of polymeric multicoordinating ligands based on the N-heterocyclic carbene (NHC) anchoring molecules and applied them for stabilizing luminescent quantum dots in aqueous media. The ligand is synthesized via nucleophilic addition reaction between amine-appended imidazole/poly(ethylene glycol) compounds and poly(isobutylene-alt-maleic anhydride) (PIMA), which yields coordinating ligands with tunable number of lateral motifs. We find that these NHC-based polymers exhibit fast and robust coordinating affinity to CdSe QDs overcoated with ZnS shells. The removal of pristine coating and the generation of carbene are demonstrated by NMR techniques. 13C and HMBC NMR spectroscopy also confirm the existence of the carbene-carbon which is crucial for binding the transition-metals on QD surfaces. These QDs exhibit essentially identical absorption and emission features before and after the cap exchange, and their compact architecture is demonstrated by diffusion ordered NMR spectroscopy. Agarose gel electrophoresis measurements indicate that the polymer coating imparts the QDs good compatibility in different pH, and it prevents protein adsorption. Excellent colloidal stability of these QD samples is observed in a wide range of competitive conditions over extended period of time. In Chapter 4, we detail the design of a set of polymeric contrast agents used for 19F magnetic resonance imaging (19F MRI). The agent is synthesized via a nucleophilic addition reaction between poly(isobutylene-alt-maleic anhydride) and amine-appended fluorinated precursors and short polyethylene glycol (PEG) coils, which permits the tunability of the stoichiometric architecture. We find that introducing PEG moieties to ~70% of the repeating units on the polymers is essential for balancing the hydrophobic feature of fluorine groups. We show that the signal to noise ratio (SNR) of the contrast agents is highly dependent on the arm-length between the polymer scaffold and the magnetic responding CF3 groups. A series of lateral fluorinated chains with different lengths are installed onto the polymers, and extended transverse relaxation time (T2) is observed from the agents with long arm-lengths. Data from Diffusion-ordered NMR spectroscopy (DOSY) indicate that using a pegylated arm between the macromolecule and CF3 groups does not greatly increase the hydrodynamic size of the resulting contrast agents. The effectiveness of inserting the arm is also confirmed by phantom images collected from agent dispersions with different concentrations. In Chapter 5, we provide a summary of the versatility of PIMA platform and discuss the outlook of these multifunctional polymeric molecules.