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 prevention of surface fouling is becoming increasingly important for the development of anti‐infective medical implants, biosensors with improved signal‐to‐noise ratios, and low‐fouling membranes ...to name a few examples. We review a direct comparison of poly(ethylene glycol), the gold standard polymer to impart surfaces with nonfouling properties, to an alternative polymer, poly(2‐methyl‐2‐oxazoline) (PMOXA), and show that both polymers are equally excellent in rendering surfaces nonfouling while PMOXA coatings are more stable in oxidative environments. We discuss prerequisites for the fabrication of nonfouling surface coatings and implications for the polymer choice according to application requirements.
We review a direct, quantitative comparison of nonfouling surface coatings based on poly(ethylene glycol) to poly(2‐methyl‐2‐oxazoline). We find that poly(2‐methyl‐2‐oxazoline) is more stable in oxidative environments, while both polymers show a similar excellent repellency of full serum proteins and bacteria. Polymer brush chain density and stretching seems to be the decisive factor rather than the nature of the polymer.
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.
Abstract Tissue engineering using scaffold-cell constructs holds the potential to develop functional strategies to regenerate bone. The interface of orthopedic implants with the host tissues is of ...great importance for its later performance. Thus, the optimization of the implant surface in a way that could stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) is of significant therapeutic interest. The effect of surface roughness of polycaprolactone (PCL) on the osteogenic differentiation of human bone-marrow MSCs was investigated. We prepared surface roughness gradients of average roughness (Ra) varying from the sub-micron to the micrometer range (∼0.5–4.7 μm), and mean distance between peaks (RS m ) gradually varying from ∼214 μm to 33 μm. We analyzed the degree of cytoskeleton spreading, expression of alkaline phosphatase, collagen type 1 and mineralization. The response of cells to roughness divided the gradient into three groups of elicited stem cell behavior: 1) faster osteogenic commitment and strongest osteogenic expression; 2) slower osteogenic commitment but strong osteogenic expression, and 3) similar or inferior osteogenic potential in comparison to the control material. The stem-cell modulation by specific PCL roughness surfaces highlights the potential for creating effective solutions for orthopedic applications featuring a clinically relevant biodegradable material.
The ability to produce patterns of single or multiple cells through precise surface engineering of cell culture substrates has promoted the development of cellular bioassays that provide entirely new ...insights into the factors that control cell adhesion to material surfaces, cell proliferation, differentiation and molecular signaling pathways. The ability to control shape and spreading of attached cells and cell–cell contacts through the form and dimension of the cell-adhesive patches with high precision is important. Commitment of stem cells to different specific lineages depends strongly on cell shape, implying that controlled microenvironments through engineered surfaces may not only be a valuable approach towards fundamental cell-biological studies, but also of great importance for the design of cell culture substrates for tissue engineering. Furthermore, cell patterning is an important tool for organizing cells on transducers for cell-based sensing and cell-based drug discovery concepts. From a material engineering standpoint, patterning approaches have greatly profited by combining microfabrication technologies, such as photolithography, with biochemical functionalization to present to the cells biological cues in spatially controlled regions where the background is rendered non-adhesive (“non-fouling”) by suitable chemical modification. The focus of this review is on the surface engineering aspects of biologically motivated
micropatterning of two-dimensional (flat) surfaces with the aim to provide an introductory overview and critical assessment of the many techniques described in the literature. In particular, the importance of non-fouling surface chemistries, the combination of hard and soft lithography with molecular assembly techniques as well as a number of less well known, but useful patterning approaches, including direct cell writing, are discussed.
Supramolecular conformation and molecular orientation was monitored during supported lipid bilayer (SLB) formation using dual polarization interferometry (DPI). DPI was shown to enable real time ...sensitive determination of birefringence of the lipid bilayer together with thickness or refractive index (with the other a fixed value). This approach removes differences in mass loading due to anisotropy, so the mass becomes solely a function of the lipid dn/dc value. DPI measurements show highly reproducible qualitative and quantitative results for adsorption of liposomes of different lipid compositions and in buffers with or without CaCl2. The packing of solvent-free self-assembled SLBs is shown to differ from other preparation methods. Birefringence analysis accompanied by mass and thickness measurements shows characteristic features of vesicle adsorption and SLB formation kinetics previously not demonstrated by evanescent optical techniques, including indications of percolation-type rupture of clusters of liposomes on the surface and correlated adsorption kinetics induced by liposome charge repulsion. Our study demonstrates that understanding of mechanistic details for an adsorption process for which conformational changes and ordering occur can be elucidated using DPI and greatly enhanced by modeling of optical birefringence. The data is in some respects more detailed than what can be obtained with conventional biosensing techniques like surface plasmon resonance and complementary to methods such as the quartz crystal microbalance.
Particle lithography has been extensively used as a robust and cost-effective method to produce large-area, close-packed arrays of nanometer scale features. Many technological applications, including ...biosensing, require instead non-close-packed patterns in order to avoid cross-talk between the features. We present a simple, scalable, single-step particle lithography process that employs colloidal self-assembly at liquid−liquid interfaces (SALI) to fabricate regular, open particle lithography masks, where the size of the features (40 to 500 nm) and their separation can be independently controlled between 3 and 10 particle diameters. Finally we show how the process can be practically employed to produce diverse biosensing structures.
Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely used experimentally and also clinically tested in diverse areas of biology and medicine. Applications include magnetic resonance ...imaging, cell sorting, drug delivery, and hyperthermia. Physicochemical surface properties are particularly relevant in the context of achieving high colloidal nanoparticle (NP) stability and preventing agglomeration (particularly challenging in biological fluids), increasing blood circulation time, and possibly targeting specific cells or tissues through the presentation of bioligands. Traditionally, NP surfaces are sterically stabilized with hydrophilic polymeric matrices, such as dextran or linear poly(ethylene glycol) brushes. While dendrimers have found applications as drug carriers, dispersants with dendritic (“dendrons”) or hyperbranched structures have been comparatively neglected despite their unique properties, such as a precisely defined molecular structure and the ability to present biofunctionalities at high density at the NP periphery. This work covers the synthesis of SPIONs and their stabilization based on poly(ethylene glycol) (PEG) and oligo(ethylene glycol) (OEG) chemistry and compares the physicochemical properties of NPs stabilized with linear and dendritic macromolecules of comparable molecular weight. The results highlight the impact of the polymeric interface architecture on solubility, colloidal stability, hydrodynamic radius, and thermoresponsive behavior. Dendron-stabilized NPs were found to provide excellent colloidal stability, despite a smaller hydrodynamic radius and lower degree of soft shell hydration compared to linear PEG analogues. Moreover, for the same grafting density and molecular weight of the stabilizers, OEG dendron-stabilized NPs show a reversible temperature-induced aggregation behavior, in contrast to the essentially irreversible aggregation and sedimentation observed for the linear PEG analogues. This new class of dendritically stabilized NPs is believed to have a potential for future biomedical and other applications, in which stability, resistance to (or reversible) aggregation, ultrasmall size (for crossing biological barriers or inclusion in responsive artificial membranes), and/or high corona density of (bio)active ligands are key.
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 ≈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.
Using quartz crystal microbalance ith dissipation monitoring it is shown that 9 ± 2‐nm iron oxide cores individually stabilized with biotin‐PEG(3400)‐gallol/methoxy‐PEG(550)‐gallol can be targeted with high binding affinity and excellent specificity toward recombinant VCAM‐1 chimera. Highly potent targeted magnetic resonance imaging contrast agents are demonstrated (see image).
This work covers the synthesis of second-generation, ethylene glycol dendrons covalently linked to a surface anchor that contains two, three, or four catechol groups, the molecular assembly in ...aqueous buffer on titanium oxide surfaces, and the evaluation of the resistance of the monomolecular adlayers against nonspecific protein adsorption in contact with full blood serum. The results were compared to those of a linear poly(ethylene glycol) (PEG) analogue with the same molecular weight. The adsorption kinetics as well as resulting surface coverages were monitored by ex situ spectroscopic ellipsometry (VASE), in situ optical waveguide lightmode spectroscopy (OWLS), and quartz crystal microbalance with dissipation (QCM-D) investigations. The expected compositions of the macromolecular films were verified by X-ray photoelectron spectroscopy (XPS). The results of the adsorption study, performed in a high ionic strength (“cloud-point”) buffer at room temperature, demonstrate that the adsorption kinetics increase with increasing number of catechol binding moieties and exceed the values found for the linear PEG analogue. This is attributed to the comparatively smaller and more confined molecular volume of the dendritic macromolecules in solution, the improved presentation of the catechol anchor, and/or their much lower cloud-point in the chosen buffer (close to room temperature). Interestingly, in terms of mechanistic aspects of “nonfouling” surface properties, the dendron films were found to be much stiffer and considerably less hydrated in comparison to the linear PEG brush surface, closer in their physicochemical properties to oligo(ethylene glycol) alkanethiol self-assembled monolayers than to conventional brush surfaces. Despite these differences, both types of polymer architectures at saturation coverage proved to be highly resistant toward protein adsorption. Although associated with higher synthesis costs, dendritic macromolecules are considered to be an attractive alternative to linear polymers for surface (bio)functionalization in view of their spontaneous formation of ultrathin, confluent, and nonfouling monolayers at room temperature and their outstanding ability to present functional ligands (coupled to the termini of the dendritic structure) at high surface densities.
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