Polymer Corona Research Articles

Characterization of Surface Patterning on Polymer-Grafted Nanocubes Using Atomic Force Microscopy and Force Volume Mapping.

Atomic force microscopy (AFM), in particular force spectroscopy, is a powerful tool for understanding the supramolecular structures associated with polymers grafted to surfaces, especially in regimes of low polymer density where different morphological structures are expected. In this study, we utilize force volume mapping to characterize the nanoscale surfaces of Ag nanocubes (AgNCs) grafted with a monolayer of polyethylene glycol (PEG) chains. Spatially resolved force-distance curves taken for a single AgNC were used to map surface properties, such as adhesion energy and deformation. We confirm the presence of surface octopus micelles that are localized on the corners of the AgNC, using force curves to resolve structural differences between the micelle "bodies" and "legs". Furthermore, we observe unique features of this system including a polymer corona stemming from AgNC-substrate interactions and polymer bridging stemming from particle-particle interactions.

Impact of Zwitterions on the Acidity Constant and Glucose Sensitivity of Block Copolymers with Phenylboronic Acid.

Molecular assemblies that transform in response to pH and saccharide concentration are promising nanomaterials in the field of biomedicine, and polymeric micelles of amphiphilic polymers with phenylboronic acids (PBAs) have been studied. Herein, we report the impact of zwitterions on the acidity constant for the collapse and the glucose sensitivity of a polymeric micelle produced from a diblock copolymer comprising polyacrylamides with PBA and zwitterionic carboxybetaine (PAEBB-b-PCBAAm). The diblock copolymer was synthesized through reversible addition-fragmentation chain-transfer polymerization followed by deprotection. PAEBB-b-PCBAAm produced micellar aggregates in aqueous solutions at a neutral pH, and the polymeric micelles collapsed at a pH of 11.0 because the PBA transformed into a hydroxyboronate anion. The pKa decreased in the presence of glucose owing to boronate ester formation. The PCBAAm chain significantly increased the pH at which the molecular assemblies dissociated. This is probably because the pKa of boronic acid increased through the dipolar interaction of zwitterions, and/or the zwitterionic polymer corona is valid for screening of PBA ionization and electrostatic repulsion of boronate anions. This study on the modulation of pKa through the zwitterionic interaction can facilitate the molecular design of pH- and saccharide-responsive biomaterials.

Corona Phase Molecular Recognition of Interleukin-6 Family Cytokines Using Nir Single Walled Carbon Nanotube

The Interleukin-6 (IL-6) family of cytokines regulate inflammation and play important roles in numerous biochemical pathways. Understanding the fundamental molecular recognition of these molecules with synthetic substrates is key to new biomedical technologies, including assays and sensors, therapeutics and purification methods. In this work, we use Corona Phase Molecular Recognition (CoPhMoRe) to engineer new carbon nanotubes corona phases and study nanotube binding to IL6. Library screening identifies two CoPhMoRe constructs based on carbon nanotube complexation with a p(AA68-rand-BA 16 -rand-CD 16 ) polymer (MK2) and a p(SS80-rand-BS 20 ) polymer (P14) corona phases respectively. Both exhibit KD of binding of 8.38 ng/mL and 16.7 μg/mL respectively, with MK2 construct having a response function consistent with two stage binding for IL-6. Comparative binding experiments show that both constructs appear to recognize the axially aligned alpha-helical structures present in the IL-6 and other IL-6 family cytokines. The findings from this study elucidate how nanoparticle interfaces can be designed to lock onto specific protein features, particularly alpha-helical structures, to enable molecular recognition and new types of sensing technologies.

Investigating the Impact of Hydrophobic Polymer Segments on the Self-Assembly Behavior of Supramolecular Cyclic Peptide Systems via Asymmetric-Flow Field Flow Fractionation.

The present study examines the behavior of cyclic peptide polymer conjugates that have been designed to combine their self-assembling ability via H-bonding with the properties of amphiphilic diblock copolymers. Using a combination of asymmetric flow-field flow fractionation (AF4) and small-angle neutron scattering (SANS), we have uncovered unique insight based on the population of structures established at a 24 h equilibrium profile. Our results determine that by introducing a small quantity of hydrophobicity into the conjugated polymer corona, the resulting nanotube structures exhibit low unimer dissociation which signifies enhanced stability. Furthermore, as the hydrophobicity of the polymer corona is increased, the elongation of the nanotubes is observed due to an increase in the association of unimers. This encompasses not only the H-bonding of unimers into nanotubes but also the self-assembly of single nanotubes into segmented-nanotube structures with high aspect ratios. However, this influence relies on a subtle balance between the hydrophobicity and hydrophilicity of the polymer corona. This balance is proposed to determine the solvent entropic penalty of hydrating the system, whereby the cost scales with the hydrophobic quantity. Consequently, it has been suggested that at a critical hydrophobic quantity, the solvation penalty becomes high enough such that the self-assembly of the system deviates from ordered hydrogen bonding. The association behavior is instead dominated by the hydrophobic effect which results in the undesirable formation of disordered aggregates.

Corona Phase Molecular Recognition of the Interleukin-6 (IL-6) Family of Cytokines Using nIR Fluorescent Single-Walled Carbon Nanotubes

The Interleukin-6 (IL-6) family of cytokines regulates inflammation and plays important roles in numerous biochemical pathways. Typically, cytokine levels are measured using enzyme-linked immunosorbent assay (ELISA) or western blot. However, these techniques usually require substantial processing time, cost, machinery, and specialist training. Understanding the fundamental molecular recognition mechanism of cytokines with synthetic substrates is key to developing new biomedical technologies such as assays, sensors, and therapeutics that overcome the above limitations. Herein, we use the corona phase molecular recognition (CoPhMoRe) approach to engineer new carbon nanotube constructs and study their binding to the inflammatory cytokines: IL-6, interleukin-11 (IL-11), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF). Library screening identified two polymer-based CoPhMoRe constructs consisting of single-walled carbon nanotubes complexed with p(AA68-rand-BA16-rand-CD16) polymer (MK2) or p(SS80-rand-BS20) polymer (P14) corona phases. The resulting dissociation constants (KD) were 8.38 ng/mL and 16.7 μg/mL, respectively, compared to that of the natural IL-6 receptor at ∼0.32 ng/mL. In addition, the MK2 constructs showed a nonmonotonic response function upon binding with IL-6. Comparative binding experiments suggest that both constructs appear to recognize the axially aligned α-helical structures present in the Interleukin-6 family. The findings from this study elucidate how nanoparticle interfaces, such as those produced by CoPhMoRe, can be designed to lock onto specific protein features. We find that the α-helical structure of the IL-6 family of cytokines can enable facile molecular recognition, opening the door to new types of label-free, low-cost sensing technologies.

Synergy between hydrophilic silica nanoparticles and poly(vinylpyrrolidone) for long-term foam stabilization with little energy input

The role of solid particles to act as foam and emulsion stabilizers is well known, providing long-term stability to the two-phase system. However, the ability for particles to generate large volumes of foam with little energy input (low agitation speeds and short agitation times) is difficult to achieve. Poor foamability is due to the slow particle adsorption dynamics and the high adsorption barrier at the air–water interface. In contrast, common surfactants and some surface active polymers which adsorb more readily at the air–water interface exhibit good foamability but often poor foam stability due to the mutual action of multiple destabilization mechanisms. In the current study, we reported a simple bi-component system of hydrophilic silica nanoparticles and poly(vinylpyrrolidone) (PVP) polymer to produce foams with both high foamability and foam stability via simply hand shaking for 1 min. Foams are stabilized by PVP coated silica composite nanoparticles (CPs) with a well-defined core–shell structure. The strong adsorption of PVP onto silica was demonstrated using Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), confirming the formation of an irreversibly and robust adsorbed polymer layer. To better understand the mechanisms for enhanced foamability and foam stability, the interfacial dynamics and the 2-dimensional mechanical properties of the particle-polymer network partitioned at the air–water interface were assessed. The presence of the PVP polymer corona substantially enhanced the adsorption and retention of hydrophilic silica particles at the air/water interface, while the rigid interfacial network formed by the silica nanoparticles guaranteed long-term foam stability (excess of one week), with coarsening fund to be the dominating destabilization mechanism for foam. The enhanced performance is in stark contrast to the individual components, which could only provide good foamability other than foam stability.

Microgels as globular protein model systems

Understanding globular protein adsorption to fluid interfaces, their interfacial assembly, and structural reorganization is not only important in the food industry, but also in medicine and biology. However, due to their intrinsic structural complexity, a unifying description of these phenomena remains elusive. Herein, we propose N-isopropylacrylamide microgels as a promising model system to isolate different aspects of adsorption, dilatational rheology, and interfacial structure at fluid interfaces with a wide range of interfacial tensions, and compare the results with the ones of globular proteins. In particular, the steady-state spontaneously-adsorbed interfacial pressure of microgels correlates closely to that of globular proteins, following the same power-law behavior as a function of the initial surface tension. However, the dilatational rheology of spontaneously-adsorbed microgel layers is dominated by the presence of a loosely packed polymer corona spread at the interface, and it thus exhibits a similar mechanical response as flexible, unstructured proteins, which are significantly weaker than globular ones. Finally, structurally, microgels reveal a similar spreading and flattening upon adsorption as globular proteins do. In conclusion, microgels offer interesting opportunities to act as powerful model systems to unravel the complex behavior of proteins at fluid interfaces.

Approximate Corona Phase Hamiltonian for Individual Cylindrical Nanoparticle-Polymer Interactions.

Nanoparticle surfaces, such as cylindrical nanowires and carbon nanotubes, are commonly coated with adsorbed polymer corona phases to impart solution stabilization and to control molecular interactions. These adsorbed polymer molecules (biological or otherwise), also known as the corona phase, are critical to engineering particle and molecular interactions. However, the prediction of its structure and the corresponding properties remains an unresolved problem in polymer physics. In this work, we construct a Hamiltonian describing the adsorption of an otherwise linear polymer to the surface of a cylindrical nanorod in the form of an integral equation summing up the energetic contributions corresponding to polymer bending, confinement, solvation, and electrostatics. We introduce an approximate functional that allows for the solution of the minimum energy configuration in the strongly bound limit. The functional is shown to predict the pitch and surface area of observed helical corona phases in the literature based on the surface binding energy and persistence length alone. This approximate functional also predicts and quantitatively describes the recently observed ionic strength-mediated phase transitions of charged polymer corona at carbon nanotube surfaces. The Hamiltonian and the approximate functional provide the first theoretical link between the polymer's mechanical and chemical properties and the resulting adsorbed phase configuration and therefore should find widespread utility in predicting corona phase structures around anisotropic nanoparticles.

Defined core–shell particles as the key to complex interfacial self-assembly

The two-dimensional self-assembly of colloidal particles serves as a model system for fundamental studies of structure formation and as a powerful tool to fabricate functional materials and surfaces. However, the prevalence of hexagonal symmetries in such self-assembling systems limits its structural versatility. More than two decades ago, Jagla demonstrated that core-shell particles with two interaction length scales can form complex, nonhexagonal minimum energy configurations. Based on such Jagla potentials, a wide variety of phases including cluster lattices, chains, and quasicrystals have been theoretically discovered. Despite the elegance of this approach, its experimental realization has remained largely elusive. Here, we capitalize on the distinct interfacial morphology of soft particles to design two-dimensional assemblies with structural complexity. We find that core-shell particles consisting of a silica core surface functionalized with a noncrosslinked polymer shell efficiently spread at a liquid interface to form a two-dimensional polymer corona surrounding the core. We controllably grow such shells by iniferter-type controlled radical polymerization. Upon interfacial compression, the resulting core-shell particles arrange in well-defined dimer, trimer, and tetramer lattices before transitioning into complex chain and cluster phases. The experimental phase behavior is accurately reproduced by Monte Carlo simulations and minimum energy calculations, suggesting that the interfacial assembly interacts via a pairwise-additive Jagla-type potential. By comparing theory, simulation, and experiment, we narrow the Jagla g-parameter of the system to between 0.9 and 2. The possibility to control the interaction potential via the interfacial morphology provides a framework to realize structural features with unprecedented complexity from a simple, one-component system.

Simulation of the Coronal Dynamics of Polymer-Grafted Nanoparticles.

Polymer-grafted nanoparticles (PGNPs) are an important component of many advanced materials. The interplay between the nanoparticle surface curvature and spatial confinement by neighboring chains produces a complex set of structural and dynamical behaviors in the polymer corona surrounding the nanoparticle. For example, experiments have shown that the inner portion of the corona is more stretched and relaxes more slowly than the outer region. Here, we perform systematic core-modified dissipative particle dynamics (CM-DPD) simulations and analyze the relaxation dynamics using proper orthogonal decomposition (POD) of the monomer coordinates. We find that grafted chains relax more slowly than free chains and that the relaxation time of the grafted chains scales inversely with the confinement strength. For PGNPs in a polymer melt, the relaxation processes are always Rouse-like. However, we observe either Zimm-like or Rouse-like dynamics for PGNPs in solution depending on the confinement strength.

Adsorption on Ligand-Tethered Nanoparticles.

We use coarse-grained molecular dynamics simulations to study adsorption on ligand-tethered particles. Nanoparticles with attached flexible and stiff ligands are considered. We discuss how the excess adsorption isotherm, the thickness of the polymer corona, and its morphology depend on the number of ligands, their length, the size of the core, and the interaction parameters. We investigate the adsorption-induced structural transitions of polymer coatings. The behavior of systems involving curved and flat “brushes” is compared.

Nanoparticle size distribution quantification from transmission electron microscopy (TEM) of ruthenium tetroxide stained polymeric nanoparticles

HypothesisDynamic Light Scattering (DLS) generated particle size distributions (PSD) of polymer-stabilized nanoparticles are dependent on the optimization parameters used to generate an inversion solution fit to the measured autocorrelation function. The accuracy of the DLS PSD average and polydispersity can be determined by comparing analyzed Transmission Electron Microscopy (TEM) images with the DLS results if the TEM measured sizes can be corrected for the thickness of the hydrated polymer corona that impacts particle hydrodynamics but is a collapsed, desiccated shell in the TEM images. ExperimentsNanoparticles were prepared by Flash NanoPrecipitation with either poly(ethylene glycol) (PEG) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) stabilizing polymers. Solvated nanoparticle size distributions were measured by DLS in aqueous media. The same nanoparticle dispersions were lyophilized onto TEM grids and stained by ruthenium tetroxide (RuO4) vapor to improve electron contrast. Desiccated particle size distributions were generated by measuring a minimum of 300 particle diameters in the stained TEM images. FindingsUsing our protocol for staining soft matter nanoparticles in TEM measurements, we have quantitatively analyzed the correlation between DLS and TEM generated PSDs. Average diameters disagree by the hydrated polymer corona thickness for each stabilizer due to the high-vacuum TEM environment, with 21.4 nm for PEG and 51.2 nm for HPMCAS. While corrected average diameter agrees within 10% for each technique, DLS consistently over-estimates the standard deviation of the PSD by 100% compared to the TEM measurement.

Structural Changes in Hairy Nanoparticles—Insights from Molecular Simulations

Coarse-grained molecular dynamics simulations are used to study the reorganization of mobile ligands pinned to isolated nanospheres. Three types of ligands are considered: (i) freely jointed homogeneous attractive chains (H); (ii) flexible diblock copolymers composed of inert linkers and the attractive end-groups (D1); and (iii) diblock copolymers built of inert flexible linkers and end-groups being attractive rigid-rods (D2). The impact of the type of ligands, their number, and the strength of interactions on the structure of hairy nanoparticles are discussed. It is shown that the properties of ligands determine the morphology of polymer corona. For the H-particles, the one-patchy and the core–shell particles are found, while for particles D1 and D2, the ligands aggregate into a few patches. As the number of ligands increases, more patches are formed. Rigidity of attractive groups favors the formation of higher number of patches. The ligands are regularly distributed in patches on the core surface. Two patches are almost symmetrically located on the core, three patches are placed nearly at the vertices of an equilateral triangle, and four patches lie at the vertices of a regular tetrahedron.

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery.

In this review, we outline the growing role that molecular dynamics simulation is able to play as a design tool in drug delivery. We cover both the pharmaceutical and computational backgrounds, in a pedagogical fashion, as this review is designed to be equally accessible to pharmaceutical researchers interested in what this new computational tool is capable of and experts in molecular modeling who wish to pursue pharmaceutical applications as a context for their research. The field has become too broad for us to concisely describe all work that has been carried out; many comprehensive reviews on subtopics of this area are cited. We discuss the insight molecular dynamics modeling has provided in dissolution and solubility, however, the majority of the discussion is focused on nanomedicine: the development of nanoscale drug delivery vehicles. Here we focus on three areas where molecular dynamics modeling has had a particularly strong impact: (1) behavior in the bloodstream and protective polymer corona, (2) Drug loading and controlled release, and (3) Nanoparticle interaction with both model and biological membranes. We conclude with some thoughts on the role that molecular dynamics simulation can grow to play in the development of new drug delivery systems.

Structure of Polymer-Grafted Nanoparticle Melts.

The structure of neat melts of polymer-grafted nanoparticles (GNPs) is studied via coarse-grained molecular dynamics simulations. We systematically vary the degree of polymerization and grafting density at fixed nanoparticle (NP) radius and study in detail the shape and size of the GNP coronas. For sufficiently high grafting density, chain sections close to the NP core are extended and form a dry layer. Further away from the NP, there is an interpenetration layer, where the polymer coronas of neighboring GNPs overlap and the chain sections have almost unperturbed conformations. To better understand this partitioning, we develop a two-layer model, representing the grafted polymer around an NP by spherical dry and interpenetration layers. This model quantitatively predicts that the thicknesses of the two layers depend on one universal parameter, x, the degree of overcrowding of grafted chains relative to chains in the melt. Both simulations and theory show that the chain extension free energy is nonmonotonic with increasing chain length at a fixed grafting density, with a well-defined maximum. This maximum is indicative of the crossover from the dry layer-dominated to interpenetration layer-dominated regime, and it could have profound consequences on our understanding of a variety of anomalous transport properties of these GNPs. Our theoretical approach therefore provides a facile means for understanding and designing solvent-free GNP-based materials.

Deformation of raspberry-like polymer composite particles by colloidal fusion

Raspberry-like polymer composite particles with polymer coronas were deformed to core–shell particles through the colloidal fusion method.

Distinct self-assembly aggregation patters of nanorods with decorated ends: A simple model study

Nanorods with polymer grafted ends are promising new materials with applications in distinct technological areas, including two dimensional films for optical devices. In this paper, we use extensive Langevin Dynamics simulations to study how the softness and competition of the ends change the assembled morphologies in a two-dimensional system. The polymer corona can be more or less compacted depending on factors as grafted density and solvent properties. In this way, we compare nanorods with ends modeled by a standard Lennard Jones (LJ), which represents a more compacted corona, with nanorods whose ends are composed by hard core-soft corona monomers, representing a less compacted corona. Hard core-soft corona colloids have competitive interactions, and we focus on how this competition can affect the self-assembled morphologies. We've constructed the morphology diagram for both cases and our results show that both types of nanorods go from a cluster to a percolation morphology as the density increases. However, the two morphologies displayed are completely different. For nanorods with LJ ends, we observed a transition from a nanowire structure at low density, where end-to-end connections are preferred, to a side-by-side aligned pattern at high densities. On the other hand, nanorods with core-softened ends assembled in thicker clusters at low densities, and the competition, typical in core-corona systems, leads to a porous morphology at high densities. These results indicate how the morphology can be tuned by the end properties to create structures that range from nanowires to 2D porous membranes.

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ad5). Patchy dendrimers bound to the surface of Ad5 formed a synthetic polymer corona that greatly altered various host interactions of Ad5 as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ad5 to blood coagulation factor X, one of the most critical virus–host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ad5 with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications.

Model-free description of polymer-coated gold nanoparticle dynamics in aqueous solutions obtained by Bayesian analysis of neutron spin echo data.

We present a neutron spin echo study of the nanosecond dynamics of polyethylene glycol (PEG) functionalized nanosized gold particles dissolved in D_{2}O at two temperatures and two different PEG molecular weights (400D and 2000D). The analysis of the neutron spin echo data was performed by applying a Bayesian approach to the description of time correlation function decays in terms of exponential terms, recently proved to be theoretically rigorous. This approach, which addresses in a direct way the fundamental issue of model choice in any dynamical analysis, provides here a guide to the most statistically supported way to follow the decay of the intermediate scattering functions I(Q,t) by basing on statistical grounds the choice of the number of terms required for the description of the nanosecond dynamics of the studied systems. Then, the presented analysis avoids from the start resorting to a preselected framework and can be considered as model free. By comparing the results of PEG-coated nanoparticles with those obtained in PEG2000 solutions, we were able to disentangle the translational diffusion of the nanoparticles from the internal dynamics of the polymer grafted to them, and to show that the polymer corona relaxation follows a pure exponential decay in agreement with the behavior predicted by coarse grained molecular dynamics simulations and theoretical models. This methodology has one further advantage: in the presence of a complex dynamical scenario, I(Q,t) is often described in terms of the Kohlrausch-Williams-Watts function that can implicitly represent a distribution of relaxation times. By choosing to describe the I(Q,t) as a sum of exponential functions and with the support of the Bayesian approach, we can explicitly determine when a finer-structure analysis of the dynamical complexity of the system exists according to the available data without the risk of overparametrization. The approach presented here is an effective tool that can be used in general to provide an unbiased interpretation of neutron spin echo data or whenever spectroscopy techniques yield time relaxation data curves.

Irradiation Effects on Polymer-Grafted Gold Nanoparticles for Cancer Therapy.

In the context of cancer treatment, gold nanoparticles (AuNPs) are considered as very promising radiosensitizers. Here, well-defined polymer-grafted AuNPs were synthesized and studied under gamma irradiation to better understand the involved radiosensitizing mechanisms. First, various water-soluble and well-defined thiol-functionalized homopolymers and copolymers were obtained through atom transfer radical polymerization. They were then used as ligands in the one-step synthesis of AuNPs, which resulted in stable hybrid metal-polymer nanoparticles. Second, these nano-objects were irradiated in solution by γ rays at different doses. Structures were fully characterized through size exclusion chromatography, small-angle X-ray scattering, and small-angle neutron scattering measurements, prior to and after irradiation. We were thus able to quantify and to localize radiation impacts onto the grafted polymers, revealing the production sites of reactive species around AuNPs. Both external and near-surface scissions were observed. Interestingly, the ratio between these two effects was found to vary according to the nature of polymer ligands. Medium-range and long-distance dose enhancements could not be identified from the calculated scission yields, but several mechanisms were considered to explain high yields found for near-surface scissions. Then cytotoxicity was shown to be equivalent for both nonirradiated and irradiated polymer-grafted NPs, which suggested that released polymer fragments were nontoxic. Finally, the potential to add bioactive molecules such as anticancer drugs has been explored by grafting doxorubicin onto the polymer corona. This may lead to nano-objects combining both radiosensitization and chemotherapy effects. This work is the first one to study in details the impact of radiation on radiosensitizing nano-objects combining physical, chemical, and biological analyses.