Development of a porous layer-by-layer microsphere with branched aliphatic hydrocarbon porogens.

Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation. How uniformity of pore size affects therapeutic delivery remains an area of active investigation. Herein, we characterize six branched aliphatic hydrocarbon-based porogen(s) produced to create pores in single and multilayered microspheres. The porogens are composed of biocompatible polycaprolactone, poly(lactic-co-glycolic acid), and polylactic acid polymers within porous multilayered microspheres. These serve as controlled effective drug and vaccine delivery platforms.

Plasmon-Tuned Particles for the Amplification of Surface-Enhanced Raman Scattering from Analytes.

Inelastic scattering from molecules because of vibrational modes produces unique Raman shifts, allowing these analytes to be detected with high specificity. Because Raman scattering is weak, surface-enhanced Raman scattering (SERS) has been used as a label-free technique for the detection of a variety of analytes at low concentrations. Using simple solution-based colloidal processing techniques, we have fabricated gold-coated carbon-black nanoparticles that show enhanced Raman activity. By varying the fabrication conditions, we create particles of different surface morphologies, allowing control over the peak wavelength for localized surface plasmon resonance (LSPR). By matching the LSPR wavelength to the incident laser wavelength, we get the highest signal from two model analytes, 4-nitrobenzenethiol (4-NBT) and Congo Red (CR). Our straightforward room-temperature-solution-based approach for making tunable SERS-active particles expands the range of incident radiation wavelengths that can be used for the detection of analytes using Raman scattering.

Interaction of Cyanobacteria with Nanometer and Micron Sized Polystyrene Particles in Marine and Fresh Water.

Microplastics and nanoplastics are emerging pollutants, widespread both in marine and in freshwater environments. Cyanobacteria are also ubiquitous in water and play a vital role in natural ecosystems, using photosynthesis to produce oxygen. Using photography, fluorescence microscopy and cryogenic and scanning electron microscopy (cryo-SEM, SEM) we investigated the physicochemical response of one of the most predominant seawater cyanobacteria (Synechococcus elongatus, PCC 7002) and freshwater cyanobacteria (S. elongatus Nageli PCC 7942) when exposed to 10 µm diameter polystyrene (microPS) and 100 nm diameter polystyrene (nanoPS) particles. Marine and freshwater cyanobacteria formed aggregates with the nanoPS, bound together by extracellular polymeric substances (EPS), and these aggregates sedimented. The aggregates were larger, and the sedimentation was more rapid for the marine system. Aggregate morphologies were qualitatively different for the microPS samples, with the bacteria linking up a small number of particles, all held together by EPS. There was no sedimentation in these samples. The cyanobacteria remained alive after exposure to the particles. The particle size- and salt concentration-dependent response of cyanobacteria to these anthropogenic stressors is an important factor to consider for a proper understanding of the fate of the particles as well as the bacteria.

Size Fractionation of Titania Nanoparticles in Wild Dittrichia viscosa Grown in a Native Environment.

We report a size fractionation of titania (TiO2) nanoparticles absorbed from the environment and found within wild Dittrichia viscosa plants. The nanoparticles were isolated by extraction and isolation from distinct plant organs, as well as from the corresponding rhizosphere of wild, adult plants. The collected nanoparticles were characterized by scanning transmission electron microscopy coupled with energy dispersive X-ray spectroscopy (STEM-EDS). More than 1200 TiO2 nanoparticles were analyzed by these techniques. The results indicated the presence of TiO2 nanoparticles with a wide range of sizes within the inspected plant organs and rhizospheres. Interestingly, a size selective process occurs during the internalization and translocation of these nanoparticles (e.g., foliar and root uptake), which favors the accumulation of mainly TiO2 nanoparticles with diameters <50 nm in the leaves, stems, and roots. In fact, our findings indicate that among the total number of TiO2 nanoparticles analyzed, the fraction of the particles with dimensions <50 nm were 52% of those within the rhizospheres, 88.5% of those within the roots, 90% of those within the stems, and 53% of those within the leaves. This significant difference observed in the size distribution of the TiO2 nanoparticles among the rhizosphere and the plant organs could have impacts on the food chain and further biologicals effects that are dependent on the size of the TiO2.

Single-Entity Electrochemistry of Nanoemulsion: The Nanostructural Effect on Its Electrochemical Behavior.

New electrochemical approaches have been applied to investigate nanoemulsions (NEs) for their nanostructures and the relevant electrochemical activity by single-entity electrochemistry (SEE). Herein, we make highly monodisperse NEs with ∼40 nm diameter, composed of biocompatible surfactants, castor oil as plasticizers, and ion exchangers. Dynamic light scattering (DLS) measurements with periodically varying surfactant to oil ratios provide us with a structural implication about uneven distributions of incorporating components inside NEs. To support this structural insight, we apply SEE and selectively monitor electron-transfer reactions occurring at individual NEs containing ferrocene upon each collision onto a Pt ultramicroelectrode. The quantitative analysis of the nanoelectrochemical results along with DLS and transmission electron microscopy (TEM) measurements reveal nanostructured compartments of incorporating components inside NEs and their effect on the electrochemical behavior. Indeed, a tunneling barrier inside NEs could be formed depending on the NE composition, thus determining an electrochemical behavior of NEs, which cannot be differentiated by a general morphological study such as DLS and TEM but by our SEE measurements. Furthermore, by employing the nanopipet voltammetry with an interface between two immiscible electrolyte solutions (ITIES) to mimic the NE interface, we could explicitly investigate that the electron-transfer reaction occurring inside NEs is facilitated by the ion-transfer reaction. Overall, these comprehensive electrochemical approaches enable us to elucidate the relation between structures and the electrochemical functionality of NEs and provide quantitative criteria for the proper compositions of NEs regarding their activity in the electrochemical applications. Also, this finding should be a prerequisite for suitable biomedical/electrochemical applications of NEs.

Characterization of alendronic- and undecylenic acid coated magnetic nanoparticles for the targeted delivery of rosiglitazone to subcutaneous adipose tissue.

Obesity is a state of positive energy balance where excess white adipose tissue accumulates to the detriment of metabolic health. Improving adipocyte function with systemic administration of thiazolidinediones (TZDs) improves metabolic outcomes in obesity, however TZD use is limited clinically due to undesirable side effects. Here we evaluate magnetic nanoparticles (MNPs) as a tool to target rosiglitazone (Rosi) specifically to adipose tissue. Results show Rosi can be adsorbed to MNPs (Rosi-MNPs) with hydrophobic coatings for which we present binding and release kinetics. Rosi adsorbed to MNPs retained the ability to induce PPARγ target gene expression in cells. Biodistribution analysis of radiolabeled Rosi-MNPs revealed a fat-implanted magnet significantly enhanced localization of Rosi to the targeted adipose tissue when administered by subcutaneous injection to obese mice. We propose MNPs for targeted delivery of anti-diabetic agents to superficially located subcutaneous adipose tissue.

Accuracy of available methods for quantifying the heat power generation of nanoparticles for magnetic hyperthermia.

In magnetic hyperthermia, characterising the specific functionality of magnetic nanoparticle arrangements is essential to plan the therapies by simulating maximum achievable temperatures. This functionality, i.e. the heat power released upon application of an alternating magnetic field, is quantified by means of the specific absorption rate (SAR), also referred to as specific loss power (SLP). Many research groups are currently involved in the SAR/SLP determination of newly synthesised materials by several methods, either magnetic or calorimetric, some of which are affected by important and unquantifiable uncertainties that may turn measurements into rough estimates. This paper reviews all these methods, discussing in particular sources of uncertainties, as well as their possible minimisation. In general, magnetic methods, although accurate, do not operate in the conditions of magnetic hyperthermia. Calorimetric methods do, but the easiest to implement, the initial-slope method in isoperibol conditions, derives inaccuracies coming from the lack of matching between thermal models, experimental set-ups and measuring conditions, while the most accurate, the pulse-heating method in adiabatic conditions, requires more complex set-ups.

Multipolymer microsphere delivery of SARS-CoV-2 antigens.

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. STATEMENT OF SIGNIFICANCE: Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics.

Contact transfer of engineered nanomaterials in the workplace.

This study investigates the potential spread of cadmium selenide quantum dots in laboratory environments through contact of gloves with simulated dry spills on laboratory countertops. Secondary transfer of quantum dots from the contaminated gloves to other substrates was initiated by contact of the gloves with different materials found in the laboratory. Transfer of quantum dots to these substrates was qualitatively evaluated by inspection under ultraviolet illumination. This secondary contact resulted in the delivery of quantum dots to all the evaluated substrates. The amount of quantum dots transferred was quantified by elemental analysis. The residue containing quantum dots picked up by the glove was transferred to at least seven additional sections of the pristine substrate through a series of sequential contacts. These results demonstrate the potential for contact transfer as a pathway for spreading nanomaterials throughout the workplace, and that 7-day-old dried spills are susceptible to the propagation of nanomaterials by contact transfer. As research and commercialization of engineered nanomaterials increase worldwide, it is necessary to establish safe practices to protect workers from the potential for chronic exposure to potentially hazardous materials. Similar experimental procedures to those described herein can be adopted by industries or regulatory agencies to guide the development of their nanomaterial safety programmes.

Anisotropic self-assemblies of magnetic nanoparticles: experimental evidence of low-field deviation from the linear response theory and empirical model.

The heating ability upon application of an alternating magnetic field of a system of monodisperse and non-interacting superparamagnetic nanoparticles is described by Rosensweig's model within the linear response limits. But in real applications, nanoparticle systems are rarely monodisperse or non-interacting, and predicting their heating ability is challenging, since it requires considering single-particle, inter-particle and collective effects. Herein we give experimental evidence of a collective effect that invalidates the linear response limits in self-assembled anisotropic arrangements. This effect allows tuning Néel relaxation times and, in turn, blocking temperatures, by just varying the alternating magnetic field amplitude. The analysis of the source magnetic and magnetothermal data leads to the development of an empirical model describing the modified Néel relaxation times in terms of characteristic parameters, whose physical interpretation is discussed. As a result, the dependency of Néel relaxation time on the magnetic field amplitude is assigned to a strong interaction energy contribution created locally by the ordered anisotropic assemblies. The reduction of this energy upon application of higher magnetic fields is related to the loss of preferred orientation of the magnetic moment of nanoparticles within assemblies. Remarkably, this energy contribution does not depend on particle volume distribution, so it does not contribute to widening of the energy barrier distribution of the assemblies, avoiding this detrimental effect of magnetic interactions, and contributing to an excellent heating ability. This work thus provides an analytical framework to analyze or predict the magnetic behavior and heating ability of superparamagnetic nanoparticles displaying collective effects.

Differentiation of Nanoparticles Isolated from Distinct Plant Species Naturally Growing in a Heavy Metal Polluted Site.

Leaves harvested from the plants of two different species (Dittrichia viscosa and Cichorium intybus) grown in their autogenous environment near a steel manufacturing company were characterized for naturally accumulated nanoparticles. These plant species are known to accumulate heavy metals. It was, however, unknown if these species would also accumulate these heavy metals in the form of nanoparticles. The isolated solid fractions were analyzed using dynamic light scattering, X-ray fluorescence, and transmission electron microscopy. These analyses revealed the presence of nanoparticles within the plants. The composition of nanoparticles found in each plant species is distinct: (i) for Dittrichia viscosa, the nanoparticle composition matched the heavy metal pollution anticipated from the surrounding industries; (ii) for Cichorium intybus, the nanoparticle composition was similar to the most abundant elements in the soil. The different behavior is a reflection of the phytoaccumulator characteristics of both species. This study provides the first evidence of sequestration of heavy metals in the form of nanoparticles by plants grown autogenously in polluted areas and will have implications in waste management of phytoremediation systems and in understanding the heavy metal life-cycle in the environment.

Green solvent assisted synthesis of cesium bismuth halide perovskite nanocrystals and the influences of slow and fast anion exchange rates.

Replacing lead in halide perovskites to address the concerns of their toxicity and stability has driven a recent surge in research toward alternative lead-free perovskite materials. Lead-free all inorganic cesium bismuth halide (Cs3Bi2X9) perovskite nanocrystals have attracted attention in recent years due to the air-stability and non-toxic nature of bismuth. Herein, we demonstrate a facile sonication-assisted approach for the preparation of all-inorganic cesium bismuth iodide (Cs3Bi2I9) perovskite nanocrystals (NCs) using propylene carbonate as a green, alternative solvent. The photoluminescence (PL) spectra of the Cs3Bi2X9 NCs have a peak emission that can be tuned from 410 to 550 nm by controlling the composition of the NCs through an anion exchange reaction using tetraalkylammonium halides as a source of halide ions. The rate of this anion exchange reaction is demonstrated to have a significant influence on the dimensions of the NCs obtained from the parent Cs3Bi2I9 NCs. The PL emission of these nanocrystals is predominately due to exciton recombination processes. The NCs also exhibit air-stability for at least 150 days.

Tunable functionalization of silica coated iron oxide nanoparticles achieved through a silanol-alcohol condensation reaction.

The surface properties of nanoparticles play an important role in their interactions with their surroundings. Silane reagents have been used for surface modifications to silica shells on iron oxide nanoparticles, but using these reagents presents some challenges. An alternative approach to modifying the surfaces of these silica shells was developed to impart different terminal functional groups, such as a thiol, alcohol, or carboxylic acid, through the use of alcohol-based reagents. This approach to surface functionalization of the core-shell particles was verified through chemical analyses and the attachment of gold nanoparticles. The use of the silanol-alcohol condensation reaction could be extended further to other surface functionalizations through the use of additional alcohol-based reagents.

Nano-objects for addressing the control of nanoparticle arrangement and performance in magnetic hyperthermia.

One current challenge of magnetic hyperthermia is achieving therapeutic effects with a minimal amount of nanoparticles, for which improved heating abilities are continuously pursued. However, it is demonstrated here that the performance of magnetite nanocubes in a colloidal solution is reduced by 84% when they are densely packed in three-dimensional arrangements similar to those found in cell vesicles after nanoparticle internalization. This result highlights the essential role played by the nanoparticle arrangement in heating performance, uncontrolled in applications. A strategy based on the elaboration of nano-objects able to confine nanocubes in a fixed arrangement is thus considered here to improve the level of control. The obtained specific absorption rate results show that nanoworms and nanospheres with fixed one- and two-dimensional nanocube arrangements, respectively, succeed in reducing the loss of heating power upon agglomeration, suggesting a change in the kind of nano-object to be used in magnetic hyperthermia.

New insights into the heating mechanisms and self-regulating abilities of manganite perovskite nanoparticles suitable for magnetic fluid hyperthermia.

The heating and self-regulating abilities of La(1-x)Sr(x)MnO(3+Δ) ferromagnetic nanoparticles for magnetic fluid hyperthermia are studied. The samples, synthesized by the Glycine Nitrate Process, present non-agglomerated particles but are partially constituted by polycrystalline nanoparticles, displaying average crystallite diameters ranging from 21 to 31 nm. The strontium content of these nanoparticles, between 0.14 and 0.39, is associated with non-stoichiometry effects in the materials, and both govern their Curie temperatures (T(C)), which range between 13 and 86 °C, respectively. Heating experiments carried out on samples suspended in an aqueous agarose gel and with different alternating magnetic fields derive unexpected maximum temperatures that cannot be explained on the basis of static magnetization data. The measurement of the thermal dependence of the specific absorption rate (SAR) of nanopowders by adiabatic magnetothermia reveals the existence of a dissipation peak just below T(C), which is assigned to a Hopkinson peak. This thermal dependence of SAR, together with a simple thermal model that considers a linear approximation for the heat power losses, is crucial to clarify the behavior observed in heating experiments and also to discuss the possibilities of the samples as self-regulating hyperthermia mediators. This analysis emphasizes that, for the correct design of a self-regulating system, the heat power losses determined by the surrounding conditions must be taken into account as well as the heating capacity of the magnetic nanoparticles.