We have found catechol-derivative anchor groups which possess irreversible binding affinity to iron oxide and thus can optimally disperse superparamagnetic nanoparticles under physiologic conditions. This not only leads to ultrastable iron oxide nanoparticles but also allows close control over the hydrodynamic diameter and interfacial chemistry. The latter is a crucial breakthrough to assemble functionalized magnetic nanoparticles, e.g., as targeted magnetic resonance contrast agents.

Superparamagnetic iron oxide nanoparticles (NPs) are used in a rapidly expanding number of research and practical applications in the biomedical field, including magnetic cell labeling separation and tracking, for therapeutic purposes in hyperthermia and drug delivery, and for diagnostic purposes, e.g., as contrast agents for magnetic resonance imaging. These applications require good NP stability at physiological conditions, close control over NP size and controlled surface presentation of functionalities. This review is focused on different aspects of the stability of superparamagnetic iron oxide NPs, from its practical definition to its implementation by molecular design of the dispersant shell around the iron oxide core and further on to its influence on the magnetic properties of the superparamagnetic iron oxide NPs. Special attention is given to the selection of molecular anchors for the dispersant shell, because of their importance to ensure colloidal and functional stability of sterically stabilized superparamagnetic iron oxide NPs. We further detail how dispersants have been optimized to gain close control over iron oxide NP stability, size and functionalities by independently considering the influences of anchors and the attached sterically repulsive polymer brushes. A critical evaluation of different strategies to stabilize and functionalize core-shell superparamagnetic iron oxide NPs as well as a brief introduction to characterization methods to compare those strategies is given.

The ideal nanoscale drug delivery vehicle allows control over the released dose in space and time. We demonstrate that this can be achieved by stealth liposomes comprising self-assembled superparamagnetic iron oxide nanoparticles (NPs) individually stabilized with palmityl-nitroDOPA incorporated in the lipid membrane. Alternating magnetic fields were used to control timing and dose of repeatedly released cargo from such vesicles by locally heating the membrane, which changed its permeability without major effects on the environment.

How droplet microfluidics can be used to fabricate solid-shelled microcapsules having precisely controlled release behavior is described. Glass capillary devices enable the production of monodisperse double emulsion drops, which can then be used as templates for microcapsule formation. The exquisite control afforded by microfluidics can be used to tune the compositions and geometrical characteristics of the microcapsules with exceptional precision. The use of this approach to fabricate microcapsules that only release their contents when exposed to a specific stimulus--such as a change in temperature, exposure to light, a change in the chemical environment, or an external stress--only after a prescribed time delay, and at a prescribed rate is reviewed.

Magnetic resonance imaging (MRI), a non-invasive, non-radiative technique, is thought to lead to cellular or even molecular resolution if optimized targeted MR contrast agents are introduced. This would allow diagnosing progressive diseases in early stages. Here, it is shown that the high binding affinity of poly(ethylene glycol)-gallol (PEG-gallol) allows freeze drying and re-dispersion of 9 +/- 2-nm iron oxide cores individually stabilized with approximately 9-nm-thick stealth coatings, yielding particle stability for at least 20 months. Particle size, stability, and magnetic properties of PEGylated particles are compared to Feridex, a commercially available untargeted negative MR contrast agent. Biotin-PEG(3400)-gallol/methoxy-PEG(550)-gallol stabilized nanoparticles are further functionalized with biotinylated human anti-VCAM-1 antibodies using the biotin-neutravidin linkage. Binding kinetics and excellent specificity of these nanoparticles are demonstrated using quartz crystal microbalance with dissipation monitoring (QCM-D). These MR contrast agents can be functionalized with any biotinylated ligand at controlled ligand surface density, rendering them a versatile research tool.

Monodisperse drops with diameters between 20 μm and 200 μm can be used to produce particles or capsules for many applications such as for cosmetics, food, and biotechnology. Drops composed of low viscosity fluids can be conveniently made using microfluidic devices. However, the throughput of microfluidic devices is limited and scale-up, achieved by increasing the number of devices run in parallel, can compromise the narrow drop-size distribution. In this paper, we present a microfluidic device, the millipede device, which forms drops through a static instability such that the fluid volume that is pinched off is the same every time a drop forms. As a result, the drops are highly monodisperse because their size is solely determined by the device geometry. This makes the operation of the device very robust. Therefore, the device can be scaled to a large number of nozzles operating simultaneously on the same chip; we demonstrate the operation of more than 500 nozzles on a single chip that produces up to 150 mL h of highly monodisperse drops.

A microfluidic approach is reported for the high-throughput, continuous production of giant unilamellar vesicles (GUVs) using water-in-oil-in-water double emulsion drops as templates. Importantly, these emulsion drops have ultrathin shells; this minimizes the amount of residual solvent that remains trapped within the GUV membrane, overcoming a major limitation of typical microfluidic approaches for GUV fabrication. This approach enables the formation of microdomains, characterized by different lipid compositions and structures within the GUV membranes. This work therefore demonstrates a straightforward and versatile approach to GUV fabrication with precise control over the GUV size, lipid composition and the formation of microdomains within the GUV membrane.

Successful applications of nanoparticles are often limited by insufficient nanoparticle stability due to low binding affinity of dispersants. However, excellent Fe3O4 nanoparticle stability was reported in a recent study (Nano Lett.2009940424048) that compared different catechol derivative-anchored low molecular weight dispersants. Here, we investigate mechanistic binding aspects of five different anchors from this study that showed radically different efficiencies as dispersant anchors, namely nitroDOPA, nitrodopamine, DOPA, dopamine, and mimosine, using electron paramagnetic resonance, Fourier transform infrared spectroscopy, and UV−vis spectroscopy. We demonstrate enhanced electron delocalization for nitrocatechols binding to Fe2+ compared to unsubstituted catechols if they are adsorbed on Fe3O4 surfaces. However a too high affinity of mimosine to Fe3+ was shown to lead to gradual dissolution of Fe3O4 nanoparticles through complexation followed by dissociation of the complex. Thus, the binding affinity of anchors should be optimized rather than maximized to achieve nanoparticle stability.