Esther Amstad

Ultrastable Iron Oxide Nanoparticle Colloidal Suspensions Using Dispersants with Catechol-Derived Anchor Groups

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.

Stabilization and functionalization of iron oxide nanoparticles for biomedical applications

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.

Triggered Release from Liposomes through Magnetic Actuation of Iron Oxide Nanoparticle Containing Membranes

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.

Surface Functionalization of Single Superparamagnetic Iron Oxide Nanoparticles for Targeted Magnetic Resonance Imaging

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.

25th Anniversary Article: Double Emulsion Templated Solid Microcapsules: Mechanics And Controlled Release

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.

Photo- and Thermoresponsive Polymersomes for Triggered Release†

Microfluidics: Thermo- and photoresponsive polymersomes are assembled using capillary microfluidic devices. Encapsulants can be selectively released from the thermoresponsive polymersomes if they are incubated at and above temperatures of 40 °C, whereas the photoresponsive polymersomes selectively release encapsulants if illuminated with laser light (see picture; NP = nanoparticle).

Ultrathin Shell Double Emulsion Templated Giant Unilamellar Lipid Vesicles with Controlled Microdomain Formation

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.

Nanoparticle actuated hollow drug delivery vehicles

The trend towards personalized medicine and the long-standing wish to reduce drug consumption and unwanted side effects have been the driving force behind research on drug delivery vehicles that control localization, timing and dose of released cargo. Controlling location and timing of the release allows using more potent drugs as the interaction with the right target is ensured and enables sequential drug release. A particularly desired solution allows for externally triggered release of encapsulated compounds. Externally controlled release can be accomplished if drug delivery vehicles, such as liposomes or polyelectrolyte multilayer capsules, incorporate nanoparticle (NP) actuators. However, close control over the structure of the composite material is necessary to harness this potential. This review describes the assembly and characterization of NP functionalized liposomes and polyelectrolyte multilayer capsules that allow for externally triggered cargo release. Special attention is paid to the relationship between NP stability and the assembly and performance of NP functionalized drug delivery vehicles.

Nanoscale probing of a polymer-blend thin film with tip-enhanced Raman spectroscopy.

Fundamental advances have been made in the spatially resolved chemical analysis of polymer thin films. Tip-enhanced Raman spectroscopy (TERS) is used to investigate the surface composition of a mixed polyisoprene (PI) and polystyrene (PS) thin film. High-quality TER spectra are collected from these nonresonant Raman-active polymers. A wealth of structural information is obtained, some of which cannot be acquired with conventional analytical techniques. PI and PS are identified at the surface and subsurface, respectively. Differences in the band intensities suggest strongly that the polymer layers are not uniformly thick, and that nanopores are present under the film surface. The continuous PS subsurface layer and subsurface nanopores have hitherto not been identified. These data are obtained with nanometer spatial resolution. Confocal far-field Raman spectroscopy and X-ray photoelectron spectroscopy are employed to corroborate some of the results. With routine production of highly enhancing TERS tips expected in the near future, it is predicted that TERS will be of great use for the rigorous chemical analysis of polymer and other composite systems with nanometer spatial resolution.

Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator

Crystal nuclei beaten to the punch Amorphous nanoparticles often dissolve more rapidly than their crystalline counterparts, which can be useful in applications such as drug delivery. Amstad et al. made amorphous nanoparticles from organic and inorganic compounds—even table salt—using droplets of dissolved compounds created with a microfluidic nebulator. The solvent evaporates fast enough that nanoparticles form before crystal nuclei can develop. The small particle size inhibits crystallization for periods of months Science, this issue p. 956 A nebulator produces solution drops so small that they dry and form amorphous nanoparticles before crystal nuclei can form. Amorphous nanoparticles (a-NPs) have physicochemical properties distinctly different from those of the corresponding bulk crystals; for example, their solubility is much higher. However, many materials have a high propensity to crystallize and are difficult to formulate in an amorphous structure without stabilizers. We fabricated a microfluidic nebulator that can produce amorphous NPs from a wide range of materials, even including pure table salt (NaCl). By using supersonic air flow, the nebulator produces drops that are so small that they dry before crystal nuclei can form. The small size of the resulting spray-dried a-NPs limits the probability of crystal nucleation in any given particle during storage. The kinetic stability of the a-NPs—on the order of months—is advantageous for hydrophobic drug molecules.