Synthese und Charakterisierung von magnetischen Eisenoxid-Nanopartikeln

In this thesis, single-core superparamagnetic iron oxide nanoparticles were synthesized via decomposition of iron-oleate. The impact of synthesis parameters on particle size distribution and magnetic properties were explored by exploiting design of experiment methodology. An empirical growth model presenting the dependencies of particle hydrodynamic size on reaction temperature and time and iron-oleate concentration was found. The formation of highly monodisperse particles was attributed to burst nucleation and rapidly terminating growth mechanisms. The slow decomposition of iron-oleate results in larger particles via gradual nucleation and retarded growth mechanisms. We established a robust synthesis to tailor the particle core size from 12 to 25 nm while preserving the size deviation < 10%. A model describing the change in the particle phase composition from pure Fe3O4 to a mixture of Fe3O4, FeO and an interfacial FeO-Fe3O4 phase as particle size enlarges was established. A deteriorated magnetic performance seen in large biphasic particles was related to the existence of differently oriented Fe3O4 crystalline domains in particle outer layers and paramagnetic FeO phase. The particles were transferred into water via exchanging oleic acid with polyethylene glycol. The particles show an excellent water stability and their magnetic core remained monodisperse and intact after PEGylation. They also exhibited a moderate cytotoxic effect on macrophages and no release of inflammatory or anti-inflammatory cytokines. The PEGylated particles with a mean core and hydrodynamic size of 24 and 60 nm were functionalized with Herceptin antibodies for homogeneous magnetic bioassays. The particle surface functionalization was monitored by measuring particle phase lag change using a fluxgate-based rotating magnetic field setup. The results showed that these particles, primarily relaxing via the Brownian mechanism, are a potent tracer for magnetic bioassays.Im Rahmen dieser Arbeit wurden superparamagnetische Einzelkern-Nanopartikel aus Eisenoxid durch die Zersetzung von Eisenoleat hergestellt. Der Einfluss der Syntheseparameter auf die Größenverteilung und magnetischen Eigenschaften wurde mit der statistischen Versuchsplanung analysiert. Ein empirisches Wachstumsmodel, das die Abhängigkeit der hydrodynamischen Partikelgröße von der Reaktionstemperatur, -zeit und Eisenoleat-Konzentration beschreibt, wurde abgeleitet. Eine abrupte Kernbildung sowie schnelle Beendigung der Wachstumsprozesse bedingte die Entstehung monodisperser Partikel. Die langsame Zersetzung von Eisenoleat bedingte die Synthese großer Partikel aufgrund der schrittweisen Kernbildung und verlangsamten Wachstumsprozesse. Es wurde ein robuster Syntheseprozess zur Herstellung von Partikelkernen zwischen 12 und 25 nm sowie einer Größenverteilung kleiner als 10% entwickelt. Ein Modell wurde etabliert, das den mit wachsender Partikelgröße eintretenden Phasenwechsel des Kernmaterials von einer reinen Fe3O4-Phase zu einer Mischung aus Fe3O4-und FeO-Phasen sowie einer FeO-Fe3O4-Grenzphase beschreibt. Die Verschlechterung der magnetischen Eigenschaften großer mehrphasiger Partikel wurde auf unterschiedlich orientierte Fe3O4 Domänen in den äußeren Schichten des Partikels und einer paramagnetischen FeO-Phase zurückgeführt. Der Wassertransfer der Partikel wurde über den Austausch von Ölsäure durch Polyethylenglycol realisiert. Nach der PEGylierung blieben die Partikel monodispers sowie magnetisch intakt und wiesen eine sehr gute Stabilität in Wasser auf. Ein moderater zytotoxischer Effekt auf Makrophagen sowie das Ausbleiben von inflammatorischen und anti-inflammatorischen Zytokinen wurde beobachtet. Die PEGylierten Partikel mit einem mittleren Kerndurchmesser von 24 nm sowie einem hydrodynamischen Durchmesser von 60 nm wurden für homogene magnetische Bioassays mit Herceptin funktionalisiert. Diese Funktionalisierung wurde mit Hilfe eines magnetischen Messsystems überwacht, das die Dynamik der Nanopartikel in einem rotierenden Magnetfeld misst. Die Resultate zeigten, dass die funktionalisierten Nanopartikel, die überwiegend nach dem Brown-Prozess relaxieren, geeignete Marker für Bioassays sind

Embracing Defects and Disorder in Magnetic Nanoparticles

Iron oxide nanoparticles have tremendous scientific and technological potential in a broad range of technologies, from energy applications to biomedicine. To improve their performance, single-crystalline and defect-free nanoparticles have thus far been aspired. However, in several recent studies defect-rich nanoparticles outperform their defect-free counterparts in magnetic hyperthermia and magnetic particle imaging. Here, an overview on the state-of-the-art of design and characterization of defects and resulting spin disorder in magnetic nanoparticles is presented with a focus on iron oxide nanoparticles. The beneficial impact of defects and disorder on intracellular magnetic hyperthermia performance of magnetic nanoparticles for drug delivery and cancer therapy is emphasized. Defect-engineering in iron oxide nanoparticles emerges to become an alternative approach to tailor their magnetic properties for biomedicine, as it is already common practice in established systems such as semiconductors and emerging fields including perovskite solar cells. Finally, perspectives and thoughts are given on how to deliberately induce defects in iron oxide nanoparticles and their potential implications for magnetic tracers to monitor cell therapy and immunotherapy by magnetic particle imaging

Influence of the Ion Coordination Number on Cation Exchange Reactions with Copper Telluride Nanocrystals

Cu2-xTe nanocubes were used as starting seeds to access metal telluride nanocrystals by cation exchanges at room temperature. The coordination number of the entering cations was found to play an important role in dictating the reaction pathways. The exchanges with tetrahedrally coordinated cations (i.e. with coordination number 4), such as Cd2+ or Hg2+, yielded monocrystalline CdTe or HgTe nanocrystals with Cu2-xTe/CdTe or Cu2-xTe/HgTe Janus-like heterostructures as intermediates. The formation of Janus-like architectures was attributed to the high diffusion rate of the relatively small tetrahedrally coordinated cations, which could rapidly diffuse in the Cu2-xTe NCs and nucleate the CdTe (or HgTe) phase in a preferred region of the host structure. Also, with both Cd2+ and Hg2+ ions the exchange led to wurtzite CdTe and HgTe phases rather than the more stable zinc-blende ones, indicating that the anion framework of the starting Cu2- xTe particles could be more easily deformed to match the anion framework of the metastable wurtzite structures. As hexagonal HgTe had never been reported to date, this represents another case of metastable new phases that can only be accessed by cation exchange. On the other hand, the exchanges involving octahedrally coordinated ions (i.e. with coordination number 6), such as Pb2+ or Sn2+, yielded rock-salt polycrystalline PbTe or SnTe nanocrystals with Cu2-xTe@PbTe or Cu2-xTe@SnTe core@shell architectures at the early stages of the exchange process. In this case, the octahedrally coordinated ions are probably too large to diffuse easily through the Cu2-xTe structure: their limited diffusion rate restricts their initial reaction to the surface of the nanocrystals, where cation exchange is initiated unselectively, leading to core@shell architectures.Comment: 11 pages, 7 figures in J. Am. Chem. Soc, 13 May 201

Asymmetric Assembling of Iron Oxide Nanocubes for Improving Magnetic Hyperthermia Performance

Magnetic hyperthermia (MH) based on magnetic nanoparticles (MNPs) is a promising adjuvant therapy for cancer treatment. Particle clustering leading to complex magnetic interactions affects the heat generated by MNPs during MH. The heat efficiencies, theoretically predicted, are still poorly understood because of a lack of control of the fabrication of such clusters with defined geometries and thus their functionality. This study aims to correlate the heating efficiency under MH of individually coated iron oxide nanocubes (IONCs) versus soft colloidal nanoclusters made of small groupings of nanocubes arranged in different geometries. The controlled clustering of alkyl-stabilized IONCs is achieved here during the water transfer procedure by tuning the fraction of the amphiphilic copolymer, poly(styrene-co-maleic anhydride) cumene-terminated, to the nanoparticle surface. It is found that increasing the polymer-to-nanoparticle surface ratio leads to the formation of increasingly large nanoclusters with defined geometries. When compared to the individual nanocubes, we show here that controlled grouping of nanoparticles - so-called "dimers" and "trimers" composed of two and three nanocubes, respectively - increases specific absorption rate (SAR) values, while conversely, forming centrosymmetric clusters having more than four nanocubes leads to lower SAR values. Magnetization measurements and Monte Carlo-based simulations support the observed SAR trend and reveal the importance of the dipolar interaction effect and its dependence on the details of the particle arrangements within the different clusters

Molecular structure, DNA binding mode, photophysical properties and recommendations for use of SYBR Gold

SYBR Gold is a commonly used and particularly bright fluorescent DNA stain, however, its chemical structure is unknown and its binding mode to DNA remains controversial. Here, we solve the structure of SYBR Gold by NMR and mass spectrometry to be 2-N-(3-dimethylaminopropyl)-N-propylamino]-4-2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene-1-phenyl-quinolinium and determine its extinction coefficient. We quantitate SYBR Gold binding to DNA using two complementary approaches. First, we use single-molecule magnetic tweezers (MT) to determine the effects of SYBR Gold binding on DNA length and twist. The MT assay reveals systematic lengthening and unwinding of DNA by 19.1° ± 0.7° per molecule upon binding, consistent with intercalation, similar to the related dye SYBR Green I. We complement the MT data with spectroscopic characterization of SYBR Gold. The data are well described by a global binding model for dye concentrations ≤2.5~μM, with parameters that quantitatively agree with the MT results. The fluorescence increases linearly with the number of intercalated SYBR Gold molecules up to dye concentrations of ∼2.5~μM, where quenching and inner filter effects become relevant. In summary, we provide a mechanistic understanding of DNA-SYBR Gold interactions and present practical guidelines for optimal DNA detection and quantitative DNA sensing applications using SYBR Gold

Cooperative dynamics of DNA-grafted magnetic nanoparticles optimize magnetic biosensing and coupling to DNA origami

Magnetic nanoparticles (MNPs) provide new opportunities for enzyme-free biosensing of nucleic acid biomarkers and magnetic actuation by patterning on DNA origami, yet how the DNA grafting density affects their dynamics and accessibility remains poorly understood. Here, we performed surface functionalization of MNPs with single-stranded DNA (ssDNA) via click chemistry with a tunable grafting density, which enables the encapsulation of single MNPs inside a functional polymeric layer. We used several complementary methods to show that particle translational and rotational dynamics exhibit a sigmoidal dependence on the ssDNA grafting density. At low densities, ssDNA strands adopt a coiled conformation that results in minor alterations to particle dynamics, while at high densities, they organize into polymer brushes that collectively influence particle dynamics. Intermediate ssDNA densities, where the dynamics are most sensitive to changes, show the highest magnetic biosensing sensitivity for the detection of target nucleic acids. Finally, we demonstrate that MNPs with high ssDNA grafting densities are required to efficiently couple to DNA origami. Our results establish ssDNA grafting density as a critical parameter for the functionalization of MNPs for magnetic biosensing and functionalization of DNA nanostructures

Correction to ‘Molecular structure, DNA binding mode, photophysical properties and recommendations for use of SYBR Gold’

This is a correction to: Nucleic Acids Research, Volume 49, Issue 9, 21 May 2021, Pages 5143–5158, https://doi.org/10.1093/nar/gkab26

The Dissociation Rate of Acetylacetonate Ligands Governs the Size of Ferrimagnetic Zinc Ferrite Nanocubes

Magnetic nanoparticles are critical to a broad range of applications, from medical diagnostics and therapeutics to biotechnological processes and single molecule manipulation. To advance these applications, facile and robust routes to synthesize highly magnetic nanoparticles over a wide size range are needed. Here, we demonstrate that changing the degassing temperature of thermal decomposition of metal acetylacetonate precursors from 90 to 25°C tunes the size of ferrimagnetic ZnxFe3-xO4 nanocubes from 25 to 100 nm, respectively. We show that degassing at 90°C nearly entirely removes acetylacetone ligands from the reaction, which results in an early formation of monomers and a reaction-controlled growth following LaMer\u27s model towards small nanocubes. In contrast, degassing at 25°C only partially dissociates acetylacetone ligands from the metal center and triggers a delayed formation of monomers, which leads to intermediate assembled structures made of tiny irregular crystallites and an eventual formation of large nanocubes via a diffusion-controlled growth mechanism. Using complementary techniques, we determine the substitution fraction x of Zn2+ to be in the range of 0.35-0.37. Our method reduces the complexity of the thermal decomposition method by narrowing the synthesis parameter space to a single physical parameter and enables fabrication of highly magnetic and uniform zinc ferrite nanocubes over a broad size range. The resulting particles are promising for a range of applications, from magnetic fluid hyperthermia to actuation of macromolecules

Decoupling the Characteristics of Magnetic Nanoparticles for Ultrahigh Sensitivity

Immunoassays exploiting magnetization dynamics of magnetic nanoparticles are highly promising for mix-and-measure, quantitative, and point-of-care diagnostics. However, how single-core magnetic nanoparticles can be employed to reduce particle concentration and concomitantly maximize assay sensitivity is not fully understood. Here, we design monodisperse Néel and Brownian relaxing magnetic nanocubes (MNCs) of different sizes and compositions. We provide insights into how to decouple physical properties of these MNCs to achieve an ultrahigh sensitivity. We find that a tri-component-based Zn0.06Co0.80Fe2.14O4 particles, with out-of-phase to initial magnetic susceptibility χ^\u27\u27/χ_0 ratio of 0.47 out of nominal ratio of 0.50 for thoroughly magnetically blocked particles, show the ultrahigh magnetic sensitivity by providing rich magnetic particle spectroscopy harmonics spectrum despite bearing a lower saturation magnetization value than di-component Zn0.1Fe2.9O4 with a high value of saturation magnetization. The Zn0.06Co0.80Fe2.14O4 MNCs, coated with polyethylene glycol-based ligands, show three orders of magnitude better sensitivity than commercially available particles of comparable size