Joachim Teller

Improved properties of magnetic particles by combination of different polymer materials as particle matrix

Abstract The properties of individual types of magnetic particles were improved by combining different polymer matrix materials. The hybrids of magnetic polysaccharide–polystyrene, silica–polystyrene, silica–polysaccharide, polysaccharide–poly(alkylcyanoacrylate) and polysaccharide–poly(lactic acid) particles are discussed and characterized by electrokinetic measurements and studies of their protein binding capacity. The improved properties of these magnetic particles lead to novel applications in diagnostics, molecular biology and biomedicine.

Synthesis and functionalisation of magnetic nanoparticles for hyperthermia applications.

Abstract A summary of recent developments in the synthesis, stabilisation and coating of magnetic iron oxide nanoparticles for hyperthermia applications is presented. Methods for synthesis in aqueous, organic and microemulsion systems are reviewed together with the resulting heating rates of the nanoparticles. Different stabilisation mechanisms for iron oxide nanoparticles from aqueous and organic media are discussed as intermediates for further coating and functionalisation. Coating with silica and/or polysaccharides is mainly used for design of nanoparticles especially for targeted hyperthermia application. These coatings permit versatile functionalisation as a basis for conjugating biomolecules, e.g. antibodies or peptides. Various strategies to conjugate biomolecules on the particle surface are discussed, with emphasis on methods that preserve biofunctionality after immobilisation. The efficiency of established methods such as carbodiimide coupling and oriented conjugation strategies is compared with new developments such as the bioorthogonal approaches that are based on the cycloaddition of strain-promoted alkynes with azides or nitrones. For targeted hyperthermia applications the study of the formation of a protein corona around nanoparticles with site-specific biomolecules on the surface is essential to achieve improved circulation times in the blood and reduced non-specific uptake by non-targeted organs for a high specific accumulation in the target tissue.

A novel and rapid method for quantification of magnetic nanoparticle?cell interactions using a desktop susceptometer

Activated endothelial cells (EC) are attractive prime targets for specific drug delivery using drug-carrying magnetic nanoparticles. In order to accomplish EC targeting, the interaction between magnetic particles and resting as well as activated endothelial cells must be characterized and quantified, because it will influence particle biodistribution, circulation half-time, and targeting efficacy. Here, we have quantified in vitro the interaction (adhesion/phagocytosis) between human endothelial cells and magnetite (Fe3O4) particles carrying different surface coatings with varying degrees of hydrophilicity and surface charge. Almost no adhesion was observed (about 1% or less) for three out of five particle types carrying plain dextran, carboxyl-substituted poly(ethylene glycol) and silica C18 coatings. In contrast, carboxyl-functionalized dextran and poly(ethylene glycol)-coated particles adhered or were phagocytosed to a considerable degree (58 and 26%, respectively). These clear and accurate results were obtained by measuring the magnetic response, i.e. magnetic susceptibility, from different fractions of the cell cultures as a means of determining the concentration of magnetic particles. Visible light and electron microscopy confirmed the magnetic quantification. To meet the need for a rapid yet sensitive instrument, we have developed a desktop magnetic susceptometer especially adapted for liquid samples or particles in a suspension. Despite its very high sensitivity, it is easy to operate and requires but a few seconds for a measurement. We also describe the construction and operation of this instrument.

Preparation and Characterization of Magnetic Nanospheres for in Vivo Application

New biodegradable magnetic nanospheres were synthesized for the application in the magnetic field assisted radionuclide therapy. For this purpose, superparamagnetic iron oxide cores were coated with several hydrophilic polymers, such as dextran, starch, chitosan, ficoll, polyethylene imine and polyvinylpyrrolidone. The different surface properties of these magnetic polymer nanospheres were demonstrated by a significant variation of the electrophoretic mobility of the particles in dependence on the pH-value.

Quantification of blood group A and B antibodies by flow cytometry using beads carrying A or B trisaccharides.

In the clinical management of patients receiving blood group ABO-incompatible organ allografts, it is of importance to determine the levels of blood group A and B antibodies before and after transplant. Currently used methods, which are mostly based on hemagglutination, are inexact and are associated with large intercenter variations. Here, we describe preliminary data from our efforts to establish a flow cytometry-based assay for the semiquantification of blood group A and B antibodies using beads carrying synthetic A or B trisaccharides. In agreement with previous investigations, blood group O individuals had greater levels of anti-A immunoglobulin G (IgG) than B individuals, whereas the levels of anti-A immunoglobulin M (IgM) were similar in sera from blood group O and B individuals.

Comparison of Strain-Promoted Alkyne-Azide Cycloaddition With Established Methods for Conjugation of Biomolecules to Magnetic Nanoparticles

The preservation of the bioreactivity of antibodies and proteins by immobilization on the surface of magnetic nanoparticles is essential for particle targeting applications in diagnosis and therapy. Here we compare the conjugation of a model antibody and of streptavidin to the surface of biocompatible 100 nm magnetic starch nanoparticles by strain-promoted alkyne-azide cycloaddition (SPAAC) with the established carbodiimide and maleimide chemistry. Under our reaction conditions the bioreactivity of the immobilized antibody was about 28% for the random amide bond formation using carbodiimide chemistry, the bioreactivity increased to about 61% for bioorthogonal SPAAC and to about 90% for maleimide conjugation. The same order was found for the biotin binding capacity of streptavidin, that was conjugated to the magnetic nanoparticles with the same methods. The described analytical methods are a platform for further studies with improved bioorthogonal conjugation reactions, e.g. the strain-promoted alkyne-nitrone cycloaddition (SPANC).

A Rapid Assay to Measure the Shielding of Iron Oxide Cores by the Particle Shell

The conjugation of magnetic nano- and microparticles with biomolecules and its analysis very often require a dense coating of the iron oxide to prevent any reaction with redox-sensitive molecules or ions. The shielding of the iron oxide cores in different types of magnetic particles was compared by rapid assays that are based on the analysis of redox reactions. The oxidation of cysteine to the corresponding cysteine disulfide in the presence of incompletely covered iron oxide was analyzed with Ellmans reagent. Similar results were obtained by analysis of the reduction of copper (II) to copper(I) by the magnetite containing particles under the conditions of the Bicinchoninic Acid (BCA) assay. We show the assay results for different commercially available magnetic particles in the size range of 20 nm to 30 μm and conclude that an incomplete coverage of the iron oxide cores requires the comparison with reference particles in redox-sensitive assays, e.g., for the characterization of the protein coating or of the density of functional groups on the particle surface.

Intramolecular macrocyclization of bis(5-methylthio-1,2-dithiole-3-thione)s with triethyl phosphite. A stereoselective route to macrocyclic (Z)-thioxodesaurines

Intramolecular macrocyclizations of [oligo(oxyethylene)ethylenedithio]bridged bis(5-methylthio-1,2-dithiole-3- thione)s 5a and b with P(OEt)3 in p-xylene furnished the macrocyclic thioxodesaurin (Z)-6, thioxodesaurin (E)-7 and 1,3-dithiafulvene (E)-8, respectively.