Physicochemical Properties Of Particles Research Articles

Iron Oxide Nanoparticle-Induced Neoplastic-Like Cell Transformation in Vitro Is Reduced with a Protective Amorphous Silica Coating.

Iron oxide nanoparticles (IONP) have recently surged in production and use in a wide variety of biomedical and environmental applications. However, their potential long-term health effects, including carcinogenesis, are unknown. Limited research suggests IONP can induce genotoxicity and neoplastic transformation associated with particle dissolution and release of free iron ions. "Safe by design" strategies involve the modification of particle physicochemical properties to affect subsequent adverse outcomes, such as an amorphous silica coating to reduce IONP dissolution and direct interaction with cells. We hypothesized that long-term exposure to a specific IONP (nFe2O3) would induce neoplastic-like cell transformation, which could be prevented with an amorphous silica coating (SiO2-nFe2O3). To test this hypothesis, human bronchial epithelial cells (Beas-2B) were continuously exposed to a 0.6 μg/cm2 administered a dose of nFe2O3 (∼0.58 μg/cm2 delivered dose), SiO2-nFe2O3 (∼0.55 μg/cm2 delivered dose), or gas metal arc mild steel welding fumes (GMA-MS, ∼0.58 μg/cm2 delivered dose) for 6.5 months. GMA-MS are composed of roughly 80% iron/iron oxide and were recently classified as a total human carcinogen. Our results showed that low-dose/long-term in vitro exposure to nFe2O3 induced a time-dependent neoplastic-like cell transformation, as indicated by increased cell proliferation and attachment-independent colony formation, which closely matched that induced by GMA-MS. This transformation was associated with decreases in intracellular iron, minimal changes in reactive oxygen species (ROS) production, and the induction of double-stranded DNA damage. An amorphous silica-coated but otherwise identical particle (SiO2-nFe2O3) did not induce this neoplastic-like phenotype or changes in the parameters mentioned above. Overall, the presented data suggest the carcinogenic potential of long-term nFe2O3 exposure and the utility of an amorphous silica coating in a "safe by design" hazard reduction strategy, within the context of a physiologically relevant exposure scenario (low-dose/long-term), with model validation using GMA-MS.

Physiochemical Effects of Nanoparticles on Cell Nuclear Complex Pore Transport: A Coarse-Grained Computational Model.

Understanding and controlling the interaction between nanoparticles and cell nuclei is critical to the development of the biomedical applications such as gene delivery, cellular imaging, and tumor therapy. Recent years have witnessed growing evidence that the size, shape, and the grafting density of the karyopherins ligands of nanoparticles provide a significant influence on the uptake mechanism of nanoparticles into cells; however, there is a lack of investigation into how these physical factors play a role in cellular nuclear uptake and how the nanoparticle enters the nucleus. Here, we build a computational framework to parametrically evaluate the effects of the size, shape, and the grafting density of the karyopherins ligands of designed nanoparticles on their transport through the nuclear pore complex of a cell nucleus so as to provide a novel scheme for nanoparticle design and precise nucleus-targeted therapy. Simulation results indicate that smaller spherical nanoparticles need to overcome a lower energy barrier than larger ones and also that nanoparticles with large grafting density exhibited greatly altered dynamics during the active transport process. Moreover, we observed that the shape and morphology of nanoparticles unambiguously determined their nuclear uptake pathways. Nuclear uptake is determined by an intricate interplay between physicochemical particle properties and nucleus properties. Our work provides a systematic understanding for nuclear uptake of nanoparticles, viruses, and bacteria and opens up a controllable design strategy for manipulating nanoparticle-nucleus interaction, with numerous applications in medicine, bioimaging, and biosensing.

Effect of collection methods on combustion particle physicochemical properties and their biological response in a human macrophage-like cell line

In vitro studies are a first step toward understanding the biological effects of combustion-derived particulate matter (cdPM). A vast majority of studies expose cells to cdPM suspensions, which requires a method to collect cdPM and suspend it in an aqueous media. The consequences of different particle collection methods on particle physiochemical properties and resulting biological responses are not fully understood. This study investigated the effect of two common approaches (collection on a filter and a cold plate) and one relatively new (direct bubbling in DI water) approach to particle collection. The three approaches yielded cdPM with differences in particle size distribution, surface area, composition, and oxidative potential. The directly bubbled sample retained the smallest sized particles and the bimodal distribution observed in the gas-phase. The bubbled sample contained ∼50% of its mass as dissolved species and lower molecular weight compounds, not found in the other two samples. These differences in the cdPM properties affected the biological responses in THP-1 cells. The bubbled sample showed greater oxidative potential and cellular reactive oxygen species. The scraped sample induced the greatest TNFα secretion. These findings have implications for in vitro studies of air pollution and for efforts to better understand the underlying mechanisms.

Oxidative potential of particles at a research house: Influencing factors and comparison with outdoor particles

The oxidative potential (OP) of particles can be represented by the ability of particles to generate hydroxyl radicals in an aqueous solution which can be measured with electron paramagnetic resonance (EPR) spectrometry. The oxidative potential of particles may be a more health-relevant metric than other physicochemical properties of particles. While OPEPR has been measured in several outdoor locations, it remains largely unstudied in indoor environments. Total suspended particle samples were collected at an unoccupied research house in eighteen four-day sampling events. The OPEPR of indoor particles was found to be 59% ± 30% of the OPEPR of outdoor particles on a sampling volume basis during normal indoor conditions in eight sampling events. However, OPEPR per particle mass was 3.5 ± 0.62 times higher indoors than outdoors, indicating that reactions taking place indoors likely increase OPEPR of indoor particles. In ten sampling events, indoor temperature, relative humidity (RH), air change rate (λ), and cooking activities were varied. OPEPR of indoor particles was found to be significantly influenced (in order of importance) by indoor RH, λ, and temperature. OPEPR of indoor particles was higher than OPEPR for outdoor particles when indoor RH and λ were increased. The presence of cooking activities did not appear to consistently increase OPEPR of indoor particles.

Shape of ligand immobilized particles dominates and amplifies the macrophage cytokine response to ligands.

Macrophages aid in clearing synthetic particulates introduced into the body and bridge innate and adaptive immunity through orchestrated secretion of cytokines and chemokines. While the field has made tremendous progress in understanding the effect of particle physicochemical properties on particle-macrophage interactions, it is not known how macrophage functions like cytokine production are affected while presenting active ligands on particles with altered physical properties. Moreover, it is unknown if ligand presentation through an altered particle shape can elicit differential macrophage cytokine responses and if responses are ligand dependent. Therefore, we investigated the influence of geometric particle presentation of diverse ligands, bovine serum albumin, immunoglobulin-G and ovalbumin, on macrophage inflammatory cytokine response. Our results indicate that for similar ligand densities, ligand presentation on rods enhanced production of inflammatory cytokine tumor necrosis factor-alpha (TNF-α) compared to spheres regardless of the nature of the ligand and its cellular receptor. Surprisingly, TNF-α responses were affected by ligand density in a shape-dependent manner and did not correlate to total particle-macrophage association. This study demonstrates the ability of geometric manipulation of particle ligands to alter macrophage cytokine response irrespective of the nature of the ligand.

Coal fly ash: linking immersion freezing behavior and physicochemical particle properties

Abstract. To date, only a few studies have investigated the potential of coal fly ash particles to trigger heterogeneous ice nucleation in cloud droplets. The presented measurements aim at expanding the sparse dataset and improving process understanding of how physicochemical particle properties can influence the freezing behavior of coal fly ash particles immersed in water. Firstly, immersion freezing measurements were performed with two single particle techniques, i.e., the Leipzig Aerosol Cloud Interaction Simulator (LACIS) and the SPectrometer for Ice Nuclei (SPIN). The effect of suspension time on the efficiency of the coal fly ash particles when immersed in a cloud droplet is analyzed based on the different residence times of the two instruments and employing both dry and wet particle generation. Secondly, two cold-stage setups, one using microliter sized droplets (Leipzig Ice Nucleation Array) and one using nanoliter sized droplets (WeIzmann Supercooled Droplets Observation on Microarray setup) were applied. We found that coal fly ash particles are comparable to mineral dust in their immersion freezing behavior when being dry generated. However, a significant decrease in immersion freezing efficiency was observed during experiments with wet-generated particles in LACIS and SPIN. The efficiency of wet-generated particles is in agreement with the cold-stage measurements. In order to understand the reason behind the deactivation, a series of chemical composition, morphology, and crystallography analyses (single particle mass spectrometry, scanning electron microscopy coupled with energy dispersive X-ray microanalysis, X-ray diffraction analysis) were performed with dry- and wet-generated particles. From these investigations, we conclude that anhydrous CaSO4 and CaO – which, if investigated in pure form, show the same qualitative immersion freezing behavior as observed for dry-generated coal fly ash particles – contribute to triggering heterogeneous ice nucleation at the particle–water interface. The observed deactivation in contact with water is related to changes in the particle surface properties which are potentially caused by hydration of CaSO4 and CaO. The contribution of coal fly ash to the ambient population of ice-nucleating particles therefore depends on whether and for how long particles are immersed in cloud droplets.

Selective Capture and Ingestion of Particles by Suspension-Feeding Bivalve Molluscs: A Review

Suspension-feeding bivalve molluscs are foundation species in coastal intertidal systems. The selective feeding capabilities of these animals can have a large influence on phytoplankton communities and nutrient flow to the benthos. Particle selection, including the types of particles chosen for ingestion and the possible mechanisms mediating selection, has been studied extensively and reported in the literature. To date, however, the possible mechanisms mediating these selective processes have remained elusive. Generally, the focus on a few key commercial species, and their demonstrated range of selective capabilities, has made it difficult to design studies that elucidate the mechanisms behind particle selection. This review focuses on key research that has been carried out in the last 20 y toward better understanding the mechanism that underlays selective capture and ingestion of particles in this important group of animals. Recently, work has been completed which has advanced the field in pointing to a passive mechanism as a mediator of selection, with the interactions between the physicochemical properties of particles and the mucus covering the pallial organs most likely mediating food choice. Although no strong evidence for an immediate, active mechanism which underlies particle selection was found, avenues for future research are suggested in this review. The possible mechanisms that control capture, including qualitative precapture selection, are also summarized and discussed in depth. Methodological considerations for rigorous experiments to advance the field are also discussed, including suggestions of general guidelines for experimental designs, which will allow better comparison of findings across studies.

Influence of Physicochemical Properties of Lipopeptide Adjuvants on the Immune Response: A Rationale for Engineering a Potent Vaccine.

Adjuvant development and understanding the physicochemical properties of particles and interpreting the subsequent immunological responses is a challenge faced by many researchers in the vaccine field. We synthesized and investigated the physicochemical properties and immunogenicity of a library of multiple epitope self-adjuvant lipopeptides in a novel asymmetric arrangement. Vaccine candidates were synthesized using a combination of solid-phase peptide synthesis and copper-mediated click chemistry. In vivo studies showed that vaccine constructs containing a single OVA CD8+ T-cell epitope and two N-terminally located C16 lipid moieties were more effective at generating robust cellular immune responses compared to the same molecule containing multiple copies of the OVA CD8+ T-cell epitope with or without the C16 moieties. Furthermore, attachment of the two C16 lipids to the N-terminus provoked formation of long β-sheet fibrils and was shown to induce a higher CD8+ donor T-cell frequency and IFN-γ secretion, compared to vaccine constructs with an internal lipid placement. A regression analysis indicated that particle secondary structure had a significant impact on CD8+ donor T-cell frequency and cytolytic activity. In addition, IFN-γ production was influenced significantly by particle shape. The findings of this research will impact the future design of a vaccine intended to elicit cellular immune responses.

Abstract 547: High-density Lipoprotein Particle Diversity From Selective Combinatorial Assembly of Particle Constituents Result in a Dynamic Particle Population

Introduction: Mass spectrometry is starting to elucidate the extent of lipoprotein diversity. It is believed that HDL is comprised of proteins encoded by >100 genes and ~200 distinct lipid species in an undetermined number of combinations. Multiple proteoforms derived from a single gene contribute to particle complexity, confound proteome identification and makes differentiation of distinct subpopulations a challenge. Subtle proteoform variants can account for alterations in particle physicochemical properties and critical functions. Refining high-definition constituent identification within a structured atlas may reveal mechanism-based pathophysiology of a variety of diseases. Hypothesis: The ongoing identification of HDL constituents necessitates an effort to catalogue, categorize, map and relate entities in a framework that organizes this knowledge in a form of testable observations, explanations and predictions. Defining constituent interactions will advance knowledge and guide inquiry that enables HDL research, clinical diagnostics and subsequent therapeutic strategies. Methods: Informatic analysis of the literature produced an HDL proteome reference set. Proteome specific analysis of gene isoforms, proteolytic products, amino acid modifications and cSNPs were used to prepare a proteoform index. Theoretical tryptic peptide maps were generated and referenced to the PeptideAtlas and available published mass spec peptide lists. Results: Over 380 non-immunoglobulin proteins were identified in high-density lipoprotein fractions from human samples. A consensus-based scoring produced an “unofficial” list of 122 genes. UniProtKB was used to expand an index of potential proteoforms and derive a theoretical peptide mass library used to map empirically defined peptide spectral lists. Conclusions: Utilizing a reductionism model to HDL measurement has proven insufficient and undermines the application of Precision Medicine for CAD. Understanding the health benefits of HDL requires clinical diagnostics that captures particle diversity and population heterogeneity. Constructing a conceptual framework that unifies a constituent map is the initial step to resolving their relational context and functional consequences.

Investigation of the Molecular Structure of the “Polyacrylamide Flocculant–H2O” System from Viscosimetry Data

The dynamic viscosity of the system "polyacrylamide flocculant–H2O" has been measured in the temperature interval 277–313 K. The dependence of the particle size on the ionic force of solutions has been investigated. The quantities characterizing the physicochemical properties of particles, such as the thickness of the diffusion layer and of the hydration sheath, have been determined. The interaction energy of particles of the high-molecular-weight compound in the solution has been studied. Results of purification of model solutions of industrial wastewater have been given, which were obtained with the fractional-flocculation technique. The characteristic of the investigation method in question has been presented, the basic classes of reactants have been described, and the mode of action of the substances has been substantiated.

Oral Vaccination Through Peyer's Patches: Update on Particle Uptake.

Oral immunization has numerous advantages over parenteral administrations. In addition to ease administration, more effective pathogen elimination on the mucosa before spreading into the blood circulation, constitutes the main benefit. This is particularly true for pathogens that enter the body through the oral route. On the other hand, it is the most challenging administration route for peptides, proteins and recombinant antigens due to gastrointestinal (GI) tract, numerous barriers including the harsh environment and the inherent weak immunogenicity. In addition to the adjuvant properties, polymeric particles arise as the most promising strategy to overcome poor antigen bioavailability/ stability upon oral administration. The Peyer's patches have been considered an important structure of the gut associate lymphoid tissue (GALT) for the initiation of the immune response towards particulate oral antigens. The transport mechanism of both, nano and microparticles across intestinal mucosa, particularly throughout Peyer's patches, is discussed in this review. We provide a short and concise update (last decade) focused on the importance of particle physicochemical properties, M-cell ligands and size-dependent transport and intracellular fate concerning Peyer's patches targeted oral vaccination.

Toward the modeling of combustion reactions through discrete element method (DEM) simulations

In this work, the process of combustion of coal particles under turbulent regime in a high-temperature reaction chamber is modeled through 3D discrete element method (DEM) simulations. By assuming the occurrence of interfacial transport phenomena between the gas and solid phases, one investigates the influence of the physicochemical properties of particles on the rates of heterogeneous chemical reactions, as well as the influence of eddies present in the gas phase on the mass transport of reactants toward the coal particles surface. Moreover, by considering a simplistic chemical mechanism for the combustion process, thermochemical and kinetic parameters obtained from the simulations are employed to discuss some phenomenological aspects of the combustion process. In particular, the observed changes in the mass and volume of coal particles during the gasification and combustion steps are discussed by emphasizing the changes in the chemical structure of the coal. In addition to illustrate how DEM simulations can be used in the modeling of consecutive and parallel chemical reactions, this work also shows how heterogeneous and homogeneous chemical reactions become a source of mass and energy for the gas phase.

<i>α</i>-Pinene secondary organic aerosol at low temperature: chemical composition and implications for particle viscosity

Abstract. Chemical composition, size distributions, and degree of oligomerization of secondary organic aerosol (SOA) from α-pinene (C10H16) ozonolysis were investigated for low-temperature conditions (223 K). Two types of experiments were performed using two simulation chambers at the Karlsruhe Institute of Technology: the Aerosol Preparation and Characterization (APC) chamber, and the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) chamber. Experiment type 1 simulated SOA formation at upper tropospheric conditions: SOA was generated in the AIDA chamber directly at 223 K at 61 % relative humidity (RH; experiment termed “cold humid”, CH) and for comparison at 6 % RH (experiment termed “cold dry”, CD) conditions. Experiment type 2 simulated SOA uplifting: SOA was formed in the APC chamber at room temperature (296 K) and < 1 % RH (experiment termed “warm dry”, WD) or 21 % RH (experiment termed “warm humid”, WH) conditions, and then partially transferred to the AIDA chamber kept at 223 K, and 61 % RH (WDtoCH) or 30 % RH (WHtoCH), respectively. Precursor concentrations varied between 0.7 and 2.2 ppm α-pinene, and between 2.3 and 1.8 ppm ozone for type 1 and type 2 experiments, respectively. Among other instrumentation, a chemical ionization mass spectrometer (CIMS) coupled to a filter inlet for gases and aerosols (FIGAERO), deploying I− as reagent ion, was used for SOA chemical composition analysis. For type 1 experiments with lower α-pinene concentrations and cold SOA formation temperature (223 K), smaller particles of 100–300 nm vacuum aerodynamic diameter (dva) and higher mass fractions (> 40 %) of adducts (molecules with more than 10 carbon atoms) of α-pinene oxidation products were observed. For type 2 experiments with higher α-pinene concentrations and warm SOA formation temperature (296 K), larger particles (∼ 500 nm dva) with smaller mass fractions of adducts (< 35 %) were produced. We also observed differences (up to 20 ∘C) in maximum desorption temperature (Tmax) of individual compounds desorbing from the particles deposited on the FIGAERO Teflon filter for different experiments, indicating that Tmax is not purely a function of a compound's vapor pressure or volatility, but is also influenced by diffusion limitations within the particles (particle viscosity), interactions between particles deposited on the filter (particle matrix), and/or particle mass on the filter. Highest Tmax were observed for SOA under dry conditions and with higher adduct mass fraction; lowest Tmax were observed for SOA under humid conditions and with lower adduct mass fraction. The observations indicate that particle viscosity may be influenced by intra- and inter-molecular hydrogen bonding between oligomers, and particle water uptake, even under such low-temperature conditions. Our results suggest that particle physicochemical properties such as viscosity and oligomer content mutually influence each other, and that variation in Tmax of particle desorptions may have implications for particle viscosity and particle matrix effects. The differences in particle physicochemical properties observed between our different experiments demonstrate the importance of taking experimental conditions into consideration when interpreting data from laboratory studies or using them as input in climate models.

Effects of fuel components and combustion particle physicochemical properties on toxicological responses of lung cells

ABSTRACTThe physicochemical properties of combustion particles that promote lung toxicity are not fully understood, hindered by the fact that combustion particles vary based on the fuel and combustion conditions. Real-world combustion-particle properties also continually change as new fuels are implemented, engines age, and engine technologies evolve. This work used laboratory-generated particles produced under controlled combustion conditions in an effort to understand the relationship between different particle properties and the activation of established toxicological outcomes in human lung cells (H441 and THP-1). Particles were generated from controlled combustion of two simple biofuel/diesel surrogates (methyl decanoate and dodecane/biofuel-blended diesel (BD), and butanol and dodecane/alcohol-blended diesel (AD)) and compared to a widely studied reference diesel (RD) particle (NIST SRM2975/RD). BD, AD, and RD particles exhibited differences in size, surface area, extractable chemical mass, and the content of individual polycyclic aromatic hydrocarbons (PAHs). Some of these differences were directly associated with different effects on biological responses. BD particles had the greatest surface area, amount of extractable material, and oxidizing potential. These particles and extracts induced cytochrome P450 1A1 and 1B1 enzyme mRNA in lung cells. AD particles and extracts had the greatest total PAH content and also caused CYP1A1 and 1B1 mRNA induction. The RD extract contained the highest relative concentration of 2-ring PAHs and stimulated the greatest level of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFα) cytokine secretion. Finally, AD and RD were more potent activators of TRPA1 than BD, and while neither the TRPA1 antagonist HC-030031 nor the antioxidant N-acetylcysteine (NAC) affected CYP1A1 or 1B1 mRNA induction, both inhibitors reduced IL-8 secretion and mRNA induction. These results highlight that differences in fuel and combustion conditions affect the physicochemical properties of particles, and these differences, in turn, affect commonly studied biological/toxicological responses.

DNA-magnetic Particle Binding Analysis by Dynamic and Electrophoretic Light Scattering.

Isolation of DNA using magnetic particles is a field of high importance in biotechnology and molecular biology research. This protocol describes the evaluation of DNA-magnetic particles binding via dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Analysis by DLS provides valuable information on the physicochemical properties of particles including particle size, polydispersity, and zeta potential. The latter describes the surface charge of the particle which plays major role in electrostatic binding of materials such as DNA. Here, a comparative analysis exploits three chemical modifications of nanoparticles and microparticles and their effects on DNA binding and elution. Chemical modifications by branched polyethylenimine, tetraethyl orthosilicate and (3-aminopropyl)triethoxysilane are investigated. Since DNA exhibits a negative charge, it is expected that zeta potential of particle surface will decrease upon binding of DNA. Forming of clusters should also affect particle size. In order to investigate the efficiency of these particles in isolation and elution of DNA, the particles are mixed with DNA in low pH (~6), high ionic strength and dehydration environment. Particles are washed on magnet and then DNA is eluted by Tris-HCl buffer (pH = 8). DNA copy number is estimated using quantitative polymerase chain reaction (PCR). Zeta potential, particle size, polydispersity and quantitative PCR data are evaluated and compared. DLS is an insightful and supporting method of analysis that adds a new perspective to the process of screening of particles for DNA isolation.

Effects of Surface Properties on Particle Capture by Two Species of Suspension-Feeding Bivalve Molluscs

The capabilities of suspension-feeding bivalve molluscs to discriminately ingest particles are well known. Physicochemical properties of particles have been shown to play a role in mediating post-capture selection in these animals. In particular, particle surface charge and wettability, a proxy for hydrophobic-hydrophilic forces, can be used by different bivalve species as determinants of selection. How physicochemical factors of particles affect their capture, however, have been little studied. To investigate such interactions, a series of adhesion assays and particle capture experiments were designed. First, mucus from the gills of the blue mussel, Mytilus edulis (Linnaeus 1758), and the bay scallop, Argopecten irradians (Lamarck 1819), were isolated separately, adsorbed onto glass microscope slides, and incubated with polystyrene microspheres (10 μm) that were either untreated or covalently bound to different neoglycoproteins (NGP; N-acetyl-glucosamine, D-mannose), or bovine serum albumin (BSA). Adhesion of treated and untreated microspheres to slides with and without mucus was quantified and statistically compared. Secondly, untreated microspheres and spheres with covalently bound NGP and BSA (ranging from 2 to 10 μm in diameter) were directly delivered to the incurrent aperture of bivalves. The excurrent water was sampled, and capture efficiencies (CE) calculated. Results demonstrate that the presence of epiparticulate BSA and NGP can significantly change the surface characteristics of microspheres, but these differences had minimal effect on adhesion to mucus or CE. A notable exception was a significant reduction in CE of D-mannose-treated 2- and 3-μm diameter microspheres by mussels compared to the control spheres of the same size. Overall, results of this study suggest that mussels and scallops can efficiently capture particles with a range of physicochemical surface properties. These findings conform to previously reported effects of particle surface properties on CE of particles by suspension-feeding bivalve larvae, but not deposit feeders.

Variations of aerosol size distribution, chemical composition and optical properties from roadside to ambient environment: A case study in Hong Kong, China

This study investigated the “roadside-to-ambient” evolution of particle physicochemical and optical properties in typical urban atmospheres of Hong Kong through collection of chemically-resolved PM2.5 data and PM2.5 size distribution at a roadside and an ambient site. Roadside particle size distribution showed typical peaks in the nuclei mode (30–40 nm) while ambient measurements peaked in the Aitken mode (50–70 nm), revealing possible condensation and coagulation growth of freshly emitted particles during aging processes. Much higher levels of anthropogenic chemical components, i.e. nitrate, sulfate, ammonium, organic carbon (OC) and elemental carbon (EC), but lower levels of OC/EC and secondary inorganic aerosols (SIA)/EC ratios appeared in roadside than ambient particles. The high OC/EC and SIA/EC ratios in ambient particles implied high contributions from secondary aerosols. Black carbon (BC), a strong light absorbing material, showed large variations in optical properties when mixed with other inorganic and organic components. Particle-bound polycyclic aromatic hydrocarbons (p-PAHs), an indicator of brown carbon (BrC), showed significant UV-absorbing ability. The average BC and p-PAHs concentrations were 3.8 and 87.6 ng m−3, respectively, at the roadside, but were only 1.5 and 18.1 ng m−3 at the ambient site, suggesting BC and p-PAHs concentrations heavily driven by traffic emissions. In contrast, PM2.5 UV light absorption coefficients (babs-BrC,370nm) at the ambient site (4.2 Mm−1) and at the roadside site (4.1 Mm−1) were similar, emphasizing that particle aging processes enhanced UV light-absorbing properties, a conclusion that was also supported by the finding that the Absorption Ångström coefficient (AAC) value at UV wavelengths (AAC_UV band) at the ambient site were ∼1.7 times higher than that at the roadside. Both aqueous reaction and photochemically produced secondary organic aerosol (SOA) for ambient aerosols contributed to the peak values of babs-BrC,370nm in ambient particles at midnight and around noon, highlighting that secondary BrC had different sources and particle aging in the atmosphere affected BrC and BC properties and related aerosol light absorption.

Cellular Shuttles: Monocytes/Macrophages Exhibit Transendothelial Transport of Nanoparticles under Physiological Flow.

A major hurdle in the development of biomedical nanoparticles (NP) is understanding how they interact with complex biological systems and navigate biological barriers to arrive at pathological targets. It is becoming increasingly evident that merely controlling particle physicochemical properties may not be sufficient to mediate particle biodistribution in dynamic environments. Thus, researchers are increasingly turning toward more complex but likewise more physiological in vitro systems to study particle--cell/particle-system interactions. An emerging paradigm is to utilize naturally migratory cells to act as so-called "Trojan horses" or cellular shuttles. We report here the use of monocytes/macrophages to transport NP across a confluent endothelial cell layer using a microfluidic in vitro model. With a custom-built flow chamber, we showed that physiological shear stress, when compared to low flow or static conditions, increased NP uptake by macrophages. We further provided a mathematical explanation for the effect of flow on NP uptake, namely that the physical exposure times of NP to cells is dictated by shear stress (i.e., flow rate) and results in increased particle uptake under flow. This study was extended to a multicellular, hydrodynamic in vitro model. Because monocytes are cells that naturally translocate across biological barriers, we utilized a monocyte/macrophage cell line as cellular NP transporters across an endothelial layer. In this exploratory study, we showed that monocyte/macrophage cells adhere to an endothelial layer and dynamically interact with the endothelial cells. The monocytes/macrophages took up NP and diapedesed across the endothelial layer with NP accumulating within the cellular uropod. These data illustrate that monocytes/macrophages may therefore act as active shuttles to deliver particles across endothelial barriers.

Physical and chemical characterization of urban winter-time aerosols by mobile measurements in Helsinki, Finland

A two-week measurement campaign by a mobile laboratory van was performed in urban environments in the Helsinki metropolitan area, Finland, in winter 2012, to obtain a comprehensive view on aerosol properties and sources. The abundances and physico-chemical properties of particles varied strongly in time and space, depending on the main sources of aerosols. Four major types of winter aerosol were recognized: 1) clean background aerosol with low particle number (Ntot) and lung deposited surface area (LDSA) concentrations due to marine air flows from the Atlantic Ocean; 2) long-range transported (LRT) pollution aerosol due to air flows from eastern Europe where the particles were characterized by the high contribution of oxygenated organic aerosol (OOA) and inorganic species, particularly sulphate, but low BC contribution, and their size distribution possessed an additional accumulation mode; 3) fresh smoke plumes from residential wood combustion in suburban small houses, these particles were characterized by high biomass burning organic aerosol (BBOA) and black carbon (BC) concentrations; and 4) fresh emissions from traffic while driving on busy streets in the city centre and on the highways during morning rush hours. This aerosol was characterized by high concentration of Ntot, LDSA, small particles in the nucleation mode, as well as high hydrocarbon-like organic aerosol (HOA) and BC concentrations. In general, secondary components (OOA, NO3, NH4, and SO4) dominated the PM1 chemical composition during the LRT episode accounting for 70–80% of the PM1 mass, whereas fresh primary emissions (BC, HOA and BBOA) dominated the local traffic and wood burning emissions. The major individual particle types observed with electron microscopy analysis (TEM/EDX) were mainly related to residential wood combustion (K/S/C-rich, soot, other C-rich particles), traffic (soot, Si/Al-rich, Fe-rich), heavy fuel oil combustion in heat plants or ships (S with V-Ni-Fe), LRT pollutants (S/C-rich secondary particles) and sea salt (Na/Cl-rich). Tar balls from wood combustion were also observed, especially (∼5%) during the LRT pollution episode.

BioTM buzz.

This special issue of Bioengineering & Translational Medicine focuses on the development of bioengineered therapeutics; specifically, design and discovery approaches, delivery platforms, and synthesis and manufacturing technologies. These three areas are essential in ensuring the successful clinical translation of new biotechnologies. As such, this first BioTM Buzz will highlight an article in each of these important areas—two articles from this special issue and another from the recent literature. Design and discovery approaches are essential in isolating and selecting lead candidates that hold promise as robust therapeutics. In this issue of Bioengineering & Translational Medicine, engineers from the Jennifer Cochran lab at Stanford University describe an approach to engineer vascular endothelial growth factor (VEGF) for increased binding affinity to vascular endothelial growth factor receptor 2 (VEGFR2), which inhibits VEGF-mediated signaling and thereby reduces angiogenesis. The authors had previously reported the design of VEGF-proteins that enhance VEGF's natural antiangiogenesis properties. In the current study, high-throughput yeast surface display was used to generate highly-potent VEGF-proteins that exhibit enhanced binding affinity to VEGFR2. Enhanced binding of VEGF-variants was confirmed in mammalian cells, which also led to inhibition of VEGF-mediated cell signaling and angiogenic processes in mice. The versatile approach will find utility in the design of new therapeutics to optimize ligand–receptor interactions or to improve binding interactions for already-approved or currently investigated protein-based therapeutics in the clinic. DOI: 10.1002/btm2.10051 Biological barriers and other physiological challenges often limit the ability of therapeutics to interact optimally, or at all, with diseased tissues. Chemical engineer Julie Champion and coworkers from the Georgia Institute of Technology describe methods to systematically investigate how the physical properties of particle-based drug delivery systems influence their fate and function. The particle-based drug delivery systems that have been clinically approved or investigated each possess unique physicochemical properties; as such, defining particle properties that exhibit enhanced biological performance in humans is a significant challenge that if addressed could aid in the design of future delivery systems. In the current study, a layer-by-layer templating approach that enabled control over particle size, shape, and stiffness, while maintaining identical surface chemistry, was used to investigate the individual and combined contributions these modifications have on particle internalization by macrophages. Complex relationships between size, shape, and stiffness were revealed—for example, spherical particles of increased size exhibited reduced internalization by macrophages, while modifications to stiffness exhibited no differences in internalization. The implications described in this paper highlight how current efforts in particle-delivery must consider all physicochemical properties of particles in tandem, since the interplay between these properties and their biological performance is a complex relationship. DOI: 10.1002/btm2.10052 Synthesis and manufacturing technologies that enable the scaled-synthesis of both therapeutics and delivery platforms are a prerequisite for clinical impact. Often times, complex approaches at the lab-scale face difficulties in translation towards industrial and commercial processes. An approach developed by Eric Appel at Stanford University and collaborators including Robert Langer at the Massachusetts Institute of Technology enables the scalable manufacturing of hydrogel materials with complex viscoelastic properties. Hydrogels are widely used as a vehicle to enable the controlled release of drugs in a variety of delivery applications. However, cost issues and scalability related to consistency of the synthesized hydrogels have limited their clinical translation. In this study, hydrogels are formed by mixing polymers and hard nanoparticles (the authors report the linear scaled-synthesis of up to 15 L using this self-assembly process); since polymer adsorption to nanoparticles is transient and reversible the resulting hydrogels exhibit both shear-thinning and self-healing properties. These shear-thinning hydrogels have great potential for biotechnology applications since they can be readily injected and capable of flowing under high stress, but then form a gel when relaxed. The approach described represents a strategy that could be readily translated to enable the large-scale synthesis of hydrogels for biomedical applications, such as combination therapies relying on the delivery of drugs of distinct physical properties. Yu et al., Proc Natl Acad Sci USA. 2016; doi: 10.1073/pnas.1618156113