Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles

Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.     

Controlled Formation of a Protein Corona Composed of Denatured BSA on Upconversion Nanoparticles Improves Their Colloidal Stability

In the natural fluidic environment of a biological system, nanoparticles swiftly adsorb plasma proteins on their surface forming a “protein corona”, which profoundly and often adversely affects their residence in the systemic circulation in vivo and their interaction with cells in vitro. It has been recognized that preformation of a protein corona under controlled conditions ameliorates the protein corona effects, including colloidal stability in serum solutions. We report on the investigation of the stabilizing effects of a denatured bovine serum albumin (dBSA) protein corona formed on the surface of upconversion nanoparticles (UCNPs). UCNPs were chosen as a nanoparticle model due to their unique photoluminescent properties suitable for background-free biological imaging and sensing. UCNP surface was modified with nitrosonium tetrafluoroborate (NOBF₄) to render it hydrophilic. UCNP-NOBF₄ nanoparticles were incubated in dBSA solution to form a dBSA corona followed up by lyophilization. As produced dBSA-UCNP-NOBF₄ demonstrated high photoluminescence brightness, sustained colloidal stability after long-term storage and the reduced level of serum protein surface adsorption. These results show promise of dBSA-based nanoparticle pretreatment to improve the amiability to biological environments towards theranostic applications.     

Investigation of Protein Corona Formed around Biologically Produced Gold Nanoparticles

Although there are several research articles on the detection and characterization of protein corona on the surface of various nanoparticles, there are no detailed studies on the formation, detection, and characterization of protein corona on the surface of biologically produced gold nanoparticles (AuNPs). AuNPs were prepared from Fusarium oxysporum at two different temperatures and characterized by spectrophotometry, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDS). The zeta potential of AuNPs was determined using a Zetasizer. AuNPs were incubated with 3 different concentrations of mouse plasma, and the hard protein corona was detected first by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and then by electrospray liquid chromatography–mass spectrometry (LC-MS). The profiles were compared to AuNPs alone that served as control. The results showed that round and oval AuNPs with sizes below 50 nm were produced at both temperatures. The AuNPs were stable after the formation of the protein corona and had sizes larger than 86 nm, and their zeta potential remained negative. We found that capping agents in the control samples contained small peptides/amino acids but almost no protein(s). After hard protein corona formation, we identified plasma proteins present on the surface of AuNPs. The identified plasma proteins may contribute to the AuNPs being shielded from phagocytizing immune cells, which makes the AuNPs a promising candidate for in vivo drug delivery. The protein corona on the surface of biologically produced AuNPs differed depending on the capping agents of the individual AuNP samples and the plasma concentration.     

Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform

Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Here we report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural erythrocyte membranes, including both membrane lipids and associated membrane proteins for long-circulating cargo delivery. The structure, size and surface zeta potential, and protein contents of the erythrocyte membrane-coated nanoparticles were verified using transmission electron microscopy, dynamic light scattering, and gel electrophoresis, respectively. Mice injections with fluorophore-loaded nanoparticles revealed superior circulation half-life by the erythrocyte-mimicking nanoparticles as compared to control particles coated with the state-of-the-art synthetic stealth materials. Biodistribution study revealed significant particle retention in the blood 72 h following the particle injection. The translocation of natural cellular membranes, their associated proteins, and the corresponding functionalities to the surface of synthetic particles represents a unique approach in nanoparticle functionalization.     

Transcytosis and brain uptake of transferrin-containing nanoparticles by tuning avidity to transferrin receptor

Receptor-mediated transcytosis across the blood–brain barrier (BBB) may be a useful way to transport therapeutics into the brain. Here we report that transferrin (Tf)-containing gold nanoparticles can reach the brain parenchyma from systemic administration in mice through a receptor-mediated transcytosis pathway. This transport is aided by tuning the nanoparticle avidity to Tf receptor (TfR), which is correlated with nanoparticle size and total amount of Tf decorating the nanoparticle surface. Nanoparticles of both 45 nm and 80 nm diameter reach the brain parenchyma, and their accumulation there (visualized by silver enhancement light microscopy in combination with transmission electron microscopy imaging) is observed to be dependent on Tf content (avidity); nanoparticles with large amounts of Tf remain strongly attached to brain endothelial cells, whereas those with less Tf are capable of both interacting with TfR on the luminal side of the BBB and detaching from TfR on the brain side of the BBB. The requirement of proper avidity for nanoparticles to reach the brain parenchyma is consistent with recent behavior observed with transcytosing antibodies that bind to TfR.Effective delivery of therapeutics to the brain has remained elusive owing to many factors, including inadequate transport across the blood–brain barrier (BBB). Numerous multidisciplinary-based strategies for transporting therapeutic agents from the blood into the brain have been proposed (1), including the use of receptor-mediated transcytosis. Recently, Yu et al. (2) reported increased accumulation of antibodies to transferrin (Tf) receptor (TfR) in the brain parenchyma when the antibody affinity was reduced. In that work, antibodies with high TfR affinity bound strongly to and remained associated with TfRs in the BBB, whereas antibodies with lower TfR affinity allowed for their detachment from TfRs and subsequent release into the brain parenchyma. These results are consistent with a previous report of a low-affinity (nearly identical to Tf–TfR interaction strength) antibody that significantly accumulated in the brain parenchyma (3).Targeted nanoparticles are finding applications for the delivery of a wide variety of therapeutic agents, and several have already reached the clinical testing stage in humans (4, 5). For example, in a Phase I clinical trial, a Tf-containing nanoparticle was used to deliver siRNA to cancer patients and shown to deliver functional siRNA to melanoma tumors in a dose-dependent manner (6). The results demonstrate that Tf-containing nanoparticles can be administered safely to humans.It is well known that the avidity and receptor selectivity of targeted nanoparticles can be tuned by the choice of targeting ligand and its number density; multivalent nanoparticles can engage multiple cell surface receptors simultaneously (7, 8). When an individual targeting ligand is conjugated to a nanoparticle, the affinity of the ligand to the receptor is reduced. However, if the receptor density is such that multiple targeting ligands on the nanoparticle can bind to the receptors simultaneously, then the targeted nanoparticle avidity (9) and selectivity (8) can be increased. These effects have been illustrated in several investigations; for example, Choi et al. (9) reported the interactions of Tf-containing gold nanoparticles on both cancer cells in vitro and tumors in vivo in mice. These authors showed that the animal whole-body biodistribution of Tf-containing gold nanoparticles of ∼70 nm in diameter was independent of the Tf content, but that the amount of nanoparticles localizing in the cancer cells of solid tumors at 24 h after injection increased with increasing Tf content. Thus, the targeting ligand acts as a cell entrance facilitator rather than altering the biodistribution of the nanoparticles. This effect is now being reported for different types of targeted nanoparticles.The objective of the present study was to investigate whether the BBB transcytosis behavior of targeted nanoparticles is similar to the BBB transcytosis behavior of antibodies in the sense that the avidity must be modulated appropriately to allow receptor binding from the blood, transcytosis across the BBB, and release from the receptor into the brain parenchyma. Our expectation was that the nanoparticles would need proper avidity, size and surface charge to effectively undergo BBB transcytosis. Our research group has been involved in translating two nanoparticles from the laboratory into clinical trials. These nanoparticles are smaller than 100 nm for many reasons, including their ability to move through tissues. Here we restricted our investigation to nanoparticles in this size range.After our experimental studies were completed, another group reported that nanoparticles in the sub–100-nm range can in fact move through brain tissue, especially when they have near-neutral zeta potentials and are coated with a dense polyethylene glycol (PEG) layer (10). Moreover, nanoparticle zeta potentials that are slightly negative to near-neutral are desirable, given that highly negatively and positively charged nanoparticles are known to (i) disrupt the BBB (11), (ii) facilitate formation of protein coronas that may mask or alter the function of the targeting ligand (12), and (iii) illicit unwanted immune responses and more rapid blood clearance via increased uptake through the mononuclear phagocyte system (13). Thus, we restricted our nanoparticles to have near-neutral zeta potentials (<−15 mV, as measured in 1.5 mM KCl).We found that Tf-containing gold nanoparticles can behave similarly to antibodies in terms of receptor binding and release at the BBB. That is, if the avidity of the nanoparticles is too low, they do not significantly bind to TfR from the blood, and if the avidity is too high, they are less available for release into the brain parenchyma. Only those nanoparticles with intermediate avidity are able to effectively transcytose and be released into the brain parenchyma.     

The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo

Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.     

Serum apolipoprotein A-I depletion is causative to silica nanoparticles–induced cardiovascular damage

The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air–blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein’s regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.

Silica nanoparticles (SiNPs) have been broadly used in construction, electronics, food packaging, cosmetics, and even the biomedicine field and contribute to extensive exposure pathways of SiNPs in human life (1). There are ∼1.1 billion workers potentially exposed to silica in agricultural or industrial activities (2), and long-term occupational exposure of silica is responsible for various diseases [i.e, silicosis, tuberculosis, airway obstructive pulmonary disease, lung cancer, rheumatoid arthritis, and scleroderma (3–6)]. Occupational diseases not only have a significant impact on individual life expectancy but also lead to serious labor loss to the society (7).Recent advances have suggested that small, inhaled particles can penetrate the air–blood barrier (ABB) from the lungs to systemic circulation (8–10), and the invasion of foreign particles may have adverse effects on the cardiovascular system (11). Substantial epidemiological studies have revealed the relationship between air pollution and cardiovascular diseases (12–14); however, the interplay of cardiovascular damage and silica exposure is not well understood.Due to high surface free energy, micro- or nano-size particles tend to adsorb encountered biomacromolecules on their surfaces to form a corona (15, 16). Theoretically, particles primitively coated with pulmonary surfactants (PS) are composed of phospholipids and surfactant proteins in alveoli. During the ABB-crossing process, the composition of the protein corona may undergo drastic exchanges, both quantitatively and qualitatively (17). Thus, inhaled particles may encounter plasma proteins and further acquire a secondary corona, which may potentially remodel the surface properties of particles and influence their subsequent biokinetics and, ultimately, toxicity (18).Here, we present a toxicological mechanism of SiNPs in cardiovascular diseases and discuss the “Jekyll and Hyde” effect of their protein corona. First, the proinflammatory effect of SiNPs was markedly relieved by corona decoration due to the dysopsonin effect. Intriguingly, the adsorption of apolipoprotein A-I (Apo A-I) on SiNPs drastically depleted Apo A-I in blood, which facilitated SiNPs-induced atherosclerosis. Accordingly, supplementation of an Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. Our results demonstrated the feasibility of in vivo manipulation of the protein corona for mitigating SiNPs-induced cardiovascular damage.     

Single-molecule protein arrays enabled by scanning probe block copolymer lithography

The ability to control the placement of individual protein molecules on surfaces could enable advances in a wide range of areas, from the development of nanoscale biomolecular devices to fundamental studies in cell biology. Such control, however, remains a challenge in nanobiotechnology due to the limitations of current lithographic techniques. Herein we report an approach that combines scanning probe block copolymer lithography with site-selective immobilization strategies to create arrays of proteins down to the single-molecule level with arbitrary pattern control. Scanning probe block copolymer lithography was used to synthesize individual sub-10-nm single crystal gold nanoparticles that can act as scaffolds for the adsorption of functionalized alkylthiol monolayers, which facilitate the immobilization of specific proteins. The number of protein molecules that adsorb onto the nanoparticles is dependent upon particle size; when the particle size approaches the dimensions of a protein molecule, each particle can support a single protein. This was demonstrated with both gold nanoparticle and quantum dot labeling coupled with transmission electron microscopy imaging experiments. The immobilized proteins remain bioactive, as evidenced by enzymatic assays and antigen-antibody binding experiments. Importantly, this approach to generate single-biomolecule arrays is, in principle, applicable to many parallelized cantilever and cantilever-free scanning probe molecular printing methods.     

Optical Properties of ZnO Nanoparticles Capped with Polymers

Optical properties of ZnO nanoparticles capped with polymers were investigated. Polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) were used as capping reagents. ZnO nanoparticles were synthesized by the sol-gel method. Fluorescence and absorption spectra were measured. When we varied the timing of the addition of the polymer to the ZnO nanoparticle solution, the optical properties were drastically changed. When PEG was added to the solution before the synthesis of ZnO nanoparticles, the fluorescence intensity increased. At the same time, the total particle size increased, which indicated that PEG molecules had capped the ZnO nanoparticles. The capping led to surface passivation, which increased fluorescence intensity. However, when PEG was added to the solution after the synthesis of ZnO nanoparticles, the fluorescence and particle size did not change. When PVP was added to the solution before the synthesis of ZnO nanoparticles, aggregation of nanoparticles occurred. When PVP was added to the solution after the synthesis of ZnO nanoparticles, fluorescence and particle size increased. This improvement of optical properties is advantageous to the practical usage of ZnO nanoparticles, such as bioimaging.     

Friction mechanism of individual multilayered nanoparticles

Inorganic nanoparticles of layered [two-dimensional (2D)] compounds with hollow polyhedral structure, known as fullerene-like nanoparticles (IF), were found to have excellent lubricating properties. This behavior can be explained by superposition of three main mechanisms: rolling, sliding, and exfoliation-material transfer (third body). In order to elucidate the tribological mechanism of individual nanoparticles in different regimes, in situ axial nanocompression and shearing forces were applied to individual nanoparticles using a high resolution scanning electron microscope. Gold nanoparticles deposited onto the IF nanoparticles surface served as markers, delineating the motion of individual IF nanoparticle. It can be concluded from these experiments that rolling is an important lubrication mechanism for IF-WS(2) in the relatively low range of normal stress (0.96 ± 0.38 GPa). Sliding is shown to be relevant under slightly higher normal stress, where the spacing between the two mating surfaces does not permit free rolling of the nanoparticles. Exfoliation of the IF nanoparticles becomes the dominant mechanism at the high end of normal stress; above 1.2 GPa and (slow) shear; i.e., boundary lubrication conditions. It is argued that the modus operandi of the nanoparticles depends on their degree of crystallinity (defects); sizes; shape, and their mechanical characteristics. This study suggests that the rolling mechanism, which leads to low friction and wear, could be attained by improving the sphericity of the IF nanoparticle, the dispersion (deagglomeration) of the nanoparticles, and the smoothness of the mating surfaces.     

Defect tolerance and the effect of structural inhomogeneity in plasmonic DNA-nanoparticle superlattices

Bottom-up assemblies of plasmonic nanoparticles exhibit unique optical effects such as tunable reflection, optical cavity modes, and tunable photonic resonances. Here, we compare detailed simulations with experiment to explore the effect of structural inhomogeneity on the optical response in DNA-gold nanoparticle superlattices. In particular, we explore the effect of background environment, nanoparticle polydispersity (>10%), and variation in nanoparticle placement (∼5%). At volume fractions less than 20% Au, the optical response is insensitive to particle size, defects, and inhomogeneity in the superlattice. At elevated volume fractions (20% and 25%), structures incorporating different sized nanoparticles (10-, 20-, and 40-nm diameter) each exhibit distinct far-field extinction and near-field properties. These optical properties are most pronounced in lattices with larger particles, which at fixed volume fraction have greater plasmonic coupling than those with smaller particles. Moreover, the incorporation of experimentally informed inhomogeneity leads to variation in far-field extinction and inconsistent electric-field intensities throughout the lattice, demonstrating that volume fraction is not sufficient to describe the optical properties of such structures. These data have important implications for understanding the role of particle and lattice inhomogeneity in determining the properties of plasmonic nanoparticle lattices with deliberately designed optical properties.The rational arrangement of nanoparticles in multiple dimensions is a promising means for creating materials with novel properties not found in nature. Noble metal nanoparticles are interesting material building blocks due to their ability to amplify local fields by orders of magnitude and scatter light well below the diffraction limit. These efficient interactions with visible light are due to localized surface plasmon resonances (LSPRs), the collective oscillation of conduction electrons (1). Hierarchical arrangements of plasmonic nanoparticles have become the basis for colorimetric sensors (2, 3), subdiffraction limited waveguides (4), visible light metamaterials (5), and nanoscale lasing devices (6, 7), and the ability to adjust architecture in such materials has led to a wide variety of structures with tunable and unusual optical properties (8–12). Many of these technologies leverage the scalability and modularity of bottom-up assembly techniques, which use chemically synthesized colloidal nanoparticles as building blocks (13, 14). Unfortunately, all nanoparticle assembly techniques result in materials with structural defects across multiple length scales, including imprecise particle placement, grain boundaries, and variation in crystallite size. In addition, the nanoparticles used in these systems are inherently inhomogeneous: varying in size, shape, and radius of curvature. Although the effects of inhomogeneity have been investigated at the individual nanoparticle level (15, 16), the effects of inhomogeneity on plasmonic assemblies are not as well understood. Determining the defect resilience of emergent properties is crucial for the continued development of scalable nanomaterial devices with reproducible properties. At this point, a comprehensive understanding of how structural defects contribute to the optical response does not exist.Herein, we combine structural and optical characterization with a variety of theoretical techniques to investigate structural inhomogeneities that affect the optical properties of hierarchical plasmonic assemblies. These factors include the chemical environment of the structure, the inhomogeneity of the nanoparticle building blocks, and the displacement of nanoparticles within the lattice. We use the programmability of DNA (3, 17–22) to construct body-centered cubic (bcc) thin-film plasmonic superlattices comprising nanospheres with diameters of 10, 20, and 40 nm. We compare the optical response of these superlattices with two types of simulations: (i) Fresnel thin-film simulations based solely on volume fraction that closely mimic the experimental geometry, and (ii) rigorous electrodynamics simulations that explicitly describe structural inhomogeneities of the crystalline superlattice. In doing so, we determine that volume fraction accurately describes the plasmonic superlattices comprising plasmonic building blocks spaced at least a diameter apart, i.e., when their interactions are primarily dipolar. At volume fractions of 20% Au and above (when the particles are within a diameter), the plasmonic properties vary depending on the nanoparticle building block size. In the far field, changes in plasmonic coupling primarily result in red-shifted collective resonances. In the near field, however, simulations suggest that both nanoparticle inhomogeneity and disorder in the superlattice arrangement alter the electric-field intensity throughout the lattice. These data suggest that the plasmonic properties of elevated volume fraction superlattices are dependent on both nanoparticle size and crystal symmetry, providing a powerful means for fine-tuning the optical response.     

Green Synthesis of Magnetic Nanoparticles of Iron Oxide Using Aqueous Extracts of Lemon Peel Waste and Its Application in Anti-Corrosive Coatings

Lately, the development of green chemistry methods with high efficiency for metal nanoparticle synthesis has become a primary focus among researchers. The main goal is to find an eco-friendly technique for the production of nanoparticles. Ferro- and ferrimagnetic materials such as magnetite (Fe₃O₄) exhibit superparamagnetic behavior at a nanometric scale. Magnetic nanoparticles have been gaining increasing interest in nanoscience and nanotechnology. This interest is attributed to their physicochemical properties, particle size, and low toxicity. The present work aims to synthesize magnetite nanoparticles in a single step using extracts of green lemon Citrus Aurantifolia residues. The results produced nanoparticles of smaller size using a method that is friendlier to health and the environment, is more profitable, and can be applied in anticorrosive coatings. The green synthesis was carried out by a co-precipitation method under variable temperature conditions. The X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) characterization showed that magnetite nanoparticles were successfully obtained with a very narrow particle size distribution between 3 and 10 nm. A composite was produced with the nanoparticles and graphene to be used as a surface coating on steel. In addition, the coating’s anticorrosive behavior was evaluated through electrochemical techniques. The surface coating obtained showed good anticorrosive properties and resistance to abrasion.     

Surface tunability of nanoparticles in modulating platelet functions

Metallic nanoparticles are attractive candidates as MRI contrast agents and mediators for drug delivery, diagnostics, and therapy. Direct contact and exposure to blood circulation is common in many such applications. The consequent thrombotic response may therefore be important to study. The main objective of the present work was to study how platelet functions were changed in the presence of different nano-surface or surface capping, which may provide a measure for the safety of a nanoparticle, and also assess the use of such nanoparticles in platelet modulation. Aggregometry, ATP release reaction, flow cytometry and immune-blotting studies were performed to study platelet response to different nano-particles (iron oxide, gold and silver). For each nanoparticle surface conjugation (capping) was varied. It was found that citric acid functionalized iron oxide nanoparticles have anti-platelet activity, with a decrease in aggregation, tyrosine phosphorylation level, and granule release. On the other hand in other cases (e.g. gold nanoparticles) pro-aggregatory response was observed in the presence of nanoparticles and, in some cases, the nanoparticles behaved neutrally (e.g. for starch-coated iron oxide nanoparticles). Therefore, nanoparticles can induce antiplatelet or a pro-aggregatory response, or remain neutral depending on surface capping. A related observation is that antiplatelet drugs can be made more potent by nanoparticle conjugation.     

UNS S31603 Stainless Steel Tungsten Inert Gas Welds Made with Microparticle and Nanoparticle Oxides

The purpose of this study was to investigate the difference between tungsten inert gas (TIG) welding of austenitic stainless steel assisted by microparticle oxides and that assisted by nanoparticle oxides. SiO₂ and Al₂O₃ were used to investigate the effects of the thermal stability and the particle size of the activated compounds on the surface appearance, geometric shape, angular distortion, delta ferrite content and Vickers hardness of the UNS {"type":"entrez-protein","attrs":{"text":"S31603","term_id":"346112","term_text":"pir||S31603"}}S31603 stainless steel TIG weld. The results show that the use of SiO₂ leads to a satisfactory surface appearance compared to that of the TIG weld made with Al₂O₃. The surface appearance of the TIG weld made with nanoparticle oxide has less flux slag compared with the one made with microparticle oxide of the same type. Compared with microparticle SiO₂, the TIG welding with nanoparticle SiO₂ has the potential benefits of high joint penetration and less angular distortion in the resulting weldment. The TIG welding with nanoparticle Al₂O₃ does not result in a significant increase in the penetration or reduction of distortion. The TIG welding with microparticle or nanoparticle SiO₂ uses a heat source with higher power density, resulting in a higher ferrite content and hardness of the stainless steel weld metal. In contrast, microparticle or nanoparticle Al₂O₃ results in no significant difference in metallurgical properties compared to that of the C-TIG weld metal. Compared with oxide particle size, the thermal stability of the oxide plays a significant role in enhancing the joint penetration capability of the weld, for the UNS {"type":"entrez-protein","attrs":{"text":"S31603","term_id":"346112","term_text":"pir||S31603"}}S31603 stainless steel TIG welds made with activated oxides.     

Selectively UV-Blocking and Visibly Transparent Adhesive Films Embedded with TiO2/PMMA Hybrid Nanoparticles for Displays

To simultaneously achieve the high visible transparency and enhance the ultraviolet (UV)-blocking performance of displays, inorganic–organic hybrid nanoparticles, comprising TiO₂ as a core and poly(methyl methacrylate) (PMMA) as a shell, were uniformly incorporated into the optically clear adhesive (OCA) used in the front of a display device. The highly refractive TiO₂ nanocore could selectively scatter UV rays, which degrade the display performance, owing to the differences in the refractive indices between the inorganic particles and PMMA matrix, thereby offering an improved UV protection property to the adhesive film. Moreover, the organic PMMA nanoshell maintained the high visible light transmittance of the pristine OCA film via the prevention of particle agglomeration. To examine the effect of the PMMA nanoshell and nanoparticle size on the optical properties of the adhesive films, the OCA films embedded with only TiO₂ nanoparticles or hybrid nanoparticles with different particle sizes were prepared using a roll-to-roll process, and characterized in the range of UV and visible lights using UV-visible spectroscopy. It is experimentally revealed that the adhesive film including small TiO₂/PMMA hybrid nanoparticles at an extremely low content exhibited enhanced UV-blocking properties and increased visible light transmittance compared to that with only TiO₂ nanoparticles.     

Delineating the pathways for the site-directed synthesis of individual nanoparticles on surfaces

Although nanoparticles with exquisite properties have been synthesized for a variety of applications, their incorporation into functional devices is challenging owing to the difficulty in positioning them at specified sites on surfaces. In contrast with the conventional synthesis-then-assembly paradigm, scanning probe block copolymer lithography can pattern precursor materials embedded in a polymer matrix and synthesize desired nanoparticles on site, offering great promise for incorporating nanoparticles into devices. This technique, however, is extremely limited from a materials standpoint. To develop a materials-general method for synthesizing nanoparticles on surfaces for broader applications, a mechanistic understanding of polymer-mediated nanoparticle formation is crucial. Here, we design a four-step synthetic process that enables independent study of the two most critical steps for synthesizing single nanoparticles on surfaces: phase separation of precursors and particle formation. Using this process, we elucidate the importance of the polymer matrix in the diffusion of metal precursors to form a single nanoparticle and the three pathways that the precursors undergo to form nanoparticles. Based on this mechanistic understanding, the synthetic process is generalized to create metal (Au, Ag, Pt, and Pd), metal oxide (Fe₂O₃, Co₂O₃, NiO, and CuO), and alloy (AuAg) nanoparticles. This mechanistic understanding and resulting process represent a major advance in scanning probe lithography as a tool to generate patterns of tailored nanoparticles for integration with solid-state devices.The integration of nanoparticles into devices has enabled applications spanning sensing (1, 2), catalysis (3), electronics (2), photonics (4), and plasmonics (5, 6), but synthesizing individual nanoparticles with control over size, composition, and placement on substrates is challenging (1–3, 6, 7). With conventional approaches, nanoparticles are synthesized and subsequently positioned on a surface using techniques such as parallel printing (8), surface dewetting (9, 10), microdroplet molding (7), nanoparticle sliding (11), direct writing (4, 12, 13), and self-assembly (2, 14, 15). However, it is difficult and in most cases, impossible to use these methods to reliably make and position a single particle on a surface with nanometer-scale control.In contrast with the conventional synthesis-then-positioning paradigm, which is the basis for most single-particle device incorporation schemes, scanning probe block copolymer lithography (SPBCL) is an example of precursor positioning-then-synthesis. The technique uses concepts from the block copolymer community (16) and the positional control offered by dip-pen nanolithography (DPN) (17) to deliver attoliter volumes of a metal-coordinated block copolymer onto a surface, which then can be used to synthesize individual nanoparticles (18, 19). Importantly, SPBCL allows one to directly synthesize arbitrary patterns of single nanoparticles over large areas on a surface, which has been useful for immobilizing single proteins (20) and studying nanoparticle coalescence in situ (21). Thus far, the technique has been extensively used to synthesize Au nanoparticles, and there is one example of cadmium sulfide nanoparticle synthesis (18, 19); however, when other metals and oxides are targeted, either they typically do not form or the technique results in multiple nanoparticles per feature. One hypothesis for this observation pertains to the high mobility of gold compared with many other materials (22), which creates a barrier to getting them to coalesce into single particles under the conditions typically used to make Au nanoparticles. If the use of this technique is to be expanded, a mechanistic understanding of the nanoparticle formation process is crucial.Here, we present a study of the two most critical steps for synthesizing single nanoparticles on a surface by SPBCL, precursor phase separation and nanoparticle formation, and from this study, we develop a mechanism for particle formation, which leads to an approach for synthesizing individual nanoparticles with control over size, composition, and surface placement. Specifically, this technique is materials-general, and it allows one to synthesize a diverse class of nanoparticles, including nanoparticles composed of Au, Ag, Pt, Pd, Fe₂O₃, Co₂O₃, NiO, CuO and alloys of Au and Ag.     

Core-controlled polymorphism in virus-like particles

This study concerns the self-assembly of virus-like particles (VLPs) composed of an icosahedral virus protein coat encapsulating a functionalized spherical nanoparticle core. The recent development of efficient methods for VLP self-assembly has opened the way to structural studies. Using electron microscopy with image reconstruction, the structures of several VLPs obtained from brome mosaic virus capsid proteins and gold nanoparticles were elucidated. Varying the gold core diameter provides control over the capsid structure. The number of subunits required for a complete capsid increases with the core diameter. The packaging efficiency is a function of the number of capsid protein subunits per gold nanoparticle. VLPs of varying diameters were found to resemble to three classes of viral particles found in cells (T=1, 2, and 3). As a consequence of their regularity, VLPs form three-dimensional crystals under the same conditions as the wild-type virus. The crystals represent a form of metallodielectric material that exhibits optical properties influenced by multipolar plasmonic coupling.     

Nanoparticle Tracing during Laser Powder Bed Fusion of Oxide Dispersion Strengthened Steels

The control of nanoparticle agglomeration during the fabrication of oxide dispersion strengthened steels is a key factor in maximizing their mechanical and high temperature reinforcement properties. However, the characterization of the nanoparticle evolution during processing represents a challenge due to the lack of experimental methodologies that allow in situ evaluation during laser powder bed fusion (LPBF) of nanoparticle-additivated steel powders. To address this problem, a simulation scheme is proposed to trace the drift and the interactions of the nanoparticles in the melt pool by joint heat-melt-microstructure–coupled phase-field simulation with nanoparticle kinematics. Van der Waals attraction and electrostatic repulsion with screened-Coulomb potential are explicitly employed to model the interactions with assumptions made based on reported experimental evidence. Numerical simulations have been conducted for LPBF of oxide nanoparticle-additivated PM2000 powder considering various factors, including the nanoparticle composition and size distribution. The obtained results provide a statistical and graphical demonstration of the temporal and spatial variations of the traced nanoparticles, showing ∼55% of the nanoparticles within the generated grains, and a smaller fraction of ∼30% in the pores, ∼13% on the surface, and ∼2% on the grain boundaries. To prove the methodology and compare it with experimental observations, the simulations are performed for LPBF of a 0.005 wt % yttrium oxide nanoparticle-additivated PM2000 powder and the final degree of nanoparticle agglomeration and distribution are analyzed with respect to a series of geometric and material parameters.