Insight into Serum Protein Interactions with Functionalized Magnetic Nanoparticles in Biological Media

Surface modification with linear polymethacrylic acid (20 kDa), linear and branched polyethylenimine (25 kDa), and branched oligoethylenimine (800 Da) is commonly used to improve the function of magnetite nanoparticles (MNPs) in many biomedical applications. These polymers were shown herein to have different adsorption capacity and anticipated conformations on the surface of MNPs due to differences in their functional groups, architectures, and molecular weight. This in turn affects the interaction of MNPs surfaces with biological serum proteins (fetal bovine serum). MNPs coated with 25 kDa branched polyethylenimine were found to attract the highest amount of serum protein while MNPs coated with 20 kDa linear polymethacrylic acid adsorbed the least. The type and amount of protein adsorbed, and the surface conformation of the polymer was shown to affect the size stability of the MNPs in a model biological media (RPMI-1640). A moderate reduction in <i>r</i>₂ relaxivity was also observed for MNPs suspended in RPMI-1640 containing serum protein compared to the same particles suspended in water. However, the relaxivities following protein adsorption are still relatively high making the use of these polymer-coated MNPs as Magnetic Resonance Imaging (MRI) contrast agents feasible. This work shows that through judicious selection of functionalization polymers and elucidation of the factors governing the stabilization mechanism, the design of nanoparticles for applications in biologically relevant conditions can be improved

Investigation of the structure and magnetism in lanthanide β-triketonate tetranuclear assemblies

<p>The preparation of discrete tetranuclear lanthanide/alkali metal (Ae) assemblies bearing a tribenzoylmethane ligand (<b>L</b>H) is discussed. These assemblies have the general formula [Ln(Ae·HOEt)(<b>L</b>)₄]₂, where Ln³⁺ = Gd³⁺, Tb³⁺, Dy³⁺, Ho³⁺ and Ae⁺ = Na⁺, K⁺, Rb⁺. The coordination geometries of the lanthanide species were analyzed and compared, revealing a trend between an eight-coordinate square antiprism and triangular dodecahedron dependent on the nature of lanthanide, alkali metal, and lattice solvent. The potassium-containing analogs were also analyzed for their magnetic susceptibility.</p

Lanthanoid “Bottlebrush” Clusters: Remarkably Elongated Metal–Oxo Core Structures with Controllable Lengths

Large metal–oxo clusters consistently assume spherical or regular polyhedral morphologies rather than high-aspect-ratio structures. Access to elongated core structures has now been achieved by the reaction of lanthanoid salts with a tetrazole-functionalized calix­arene in the presence of a simple carboxylate co-ligand. The resulting Ln₁₉ and Ln₁₂ clusters are constructed from apex-fused Ln₅O₆ trigonal bipyramids and are formed consistently under a range of reaction conditions and reagent ratios. Altering the carboxylate co-ligand structure reliably controls the cluster length, giving access to a new class of rod-like clusters of variable length

Lanthanoid “Bottlebrush” Clusters: Remarkably Elongated Metal–Oxo Core Structures with Controllable Lengths

Large metal–oxo clusters consistently assume spherical or regular polyhedral morphologies rather than high-aspect-ratio structures. Access to elongated core structures has now been achieved by the reaction of lanthanoid salts with a tetrazole-functionalized calix­arene in the presence of a simple carboxylate co-ligand. The resulting Ln₁₉ and Ln₁₂ clusters are constructed from apex-fused Ln₅O₆ trigonal bipyramids and are formed consistently under a range of reaction conditions and reagent ratios. Altering the carboxylate co-ligand structure reliably controls the cluster length, giving access to a new class of rod-like clusters of variable length

Toward Design of Magnetic Nanoparticle Clusters Stabilized by Biocompatible Diblock Copolymers for <i>T</i>₂‑Weighted MRI Contrast

We report the fabrication of magnetic particles comprised of clusters of iron oxide nanoparticles, 7.4 nm mean diameter, stabilized by a biocompatible, amphiphilic diblock copolymer, poly­(ethylene oxide-<i>b</i>-d,l-lactide). Particles with quantitative incorporation of up to 40 wt % iron oxide and hydrodynamic sizes in the range of 80–170 nm were prepared. The particles consist of hydrophobically modified iron oxide nanoparticles within the core-forming polylactide block with the poly­(ethylene oxide) forming a corona to afford aqueous dispersibility. The transverse relaxivities (<i>r</i>₂) increased with average particle size and exceeded 200 s^–1 mM Fe^–1 at 1.4 T and 37 °C for iron oxide loadings above 30 wt %. These experimental relaxivities typically agreed to within 15% with the values predicted using analytical models of transverse relaxivity and cluster (particle core) size distributions derived from cryo-TEM measurements. Our results show that the theoretical models can be used for the rational design of biocompatible MRI contrast agents with tailored compositions and size distributions

<i>Schistosoma mansoni</i> egg – paramagnetic microsphere conjugates.

<p>At least 15 microspheres can be seen bound to the surface of the egg. A magnet is rotated around the suspension by 180 degrees over approximately 0.5 seconds (black arrows indicate the movement of the magnet). The images represent frame captures from <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002219#pntd.0002219.s003" target="_blank">Video S1</a> available as supporting information.</p

Morphology of <i>Schistosoma mansoni</i> and <i>Schistosoma japonicum</i> eggs.

<p>Panel A shows an intact egg of <i>S. mansoni</i>. Panel B shows an <i>S. mansoni</i> egg broken open with the miracidium still inside the egg. Panels C and D show similar images for <i>S. japonicum</i>.</p

Elemental concentration in <i>Schistosoma mansoni</i> and <i>Schistosoma japonicum</i> eggs.

<p>Elemental concentration in <i>Schistosoma mansoni</i> and <i>Schistosoma japonicum</i> eggs.</p

Microsphere binding characteristics to <i>S.</i> mansoni and <i>S. japonicum</i> eggs.

<p>Panel A shows the fraction of eggs that had at least one microsphere bound at an egg to microsphere ratio of 1∶100. Panel B shows the distribution of the number of microspheres bound to eggs of the two parasite species at an egg to microsphere ratio of 1∶100. Panels C and D show the same data for an egg to parasite ratio of 1∶500. For both ratios <i>S. japonicum</i> eggs spontaneously conjugated with microspheres at a significantly higher frequency than <i>S. mansoni</i> eggs. Similarly, the average number of microspheres per individual egg was considerably higher for <i>S. japonicum</i> than for <i>S. mansoni</i> (Panels B and D).</p

Iron localization within the <i>Schistosoma</i> eggshell.

<p>Panel A shows inclusions of iron phosphate in the shell of <i>S. mansoni</i> at low resolution. Panel B shows similar inclusions in <i>S. mansoni</i> at a higher resolution. Panel C depicts the STEM-EDS spectra for iron, phosphorous and oxygen acquired when scanning across an inclusion, along the white line (d) shown in Panel B. Panels D, E and F show similar observations for <i>S. japonicum</i>.</p