Targeted luminescent near-infrared polymer-nanoprobes for in vivo imaging of tumor hypoxia

Polystyrene nanoparticles (PS-NPs) were doped with an oxygen-sensitive near-infrared (NIR)-emissive palladium meso-tetraphenylporphyrin and an inert reference dye which are both excitable at 635 nm. The nanosensors were characterized with special emphasis on fundamental parameters such as absolute photoluminescence quantum yield and fluorescence lifetime. The PS-NPs were employed for ratiometric dual-wavelength and lifetime-based photoluminescent oxygen sensing. They were efficiently taken up by cultured murine alveolar macrophages, yielding a characteristic and reversible change in ratiometric response with decreasing oxygen concentration. This correlated with the cellular hypoxic status verified by analysis of hypoxia inducible factor-1α (HIF-1α) accumulation. In addition, the surface of PS-NPs was functionalized with polyethylene glycol (PEG) and the monoclonal antibody herceptin, and their binding to HER2/neu-overexpressing tumor cells was confirmed in vitro. First experiments with tumor-bearing mouse revealed a distinctive ratiometric response within the tumor upon hypoxic condition induced by animal sacrifice. These results demonstrate the potential of these referenced NIR nanosensors for in vitro and in vivo imaging that present a new generation of optical probes for oncology.     

Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology

Quantification of programmed and accidental cell death provides useful end-points for the anticancer drug efficacy assessment. Cell death is, however, a stochastic process. Therefore, the opportunity to dynamically quantify individual cellular states is advantageous over the commonly employed static, end-point assays. In this work, we describe the development and application of a microfabricated, dielectrophoretic (DEP) cell immobilization platform for the real-time analysis of cancer drug-induced cytotoxicity. Microelectrode arrays were designed to generate weak electro-thermal vortices that support efficient drug mixing and rapid cell immobilization at the delta-shape regions of strong electric field formed between the opposite microelectrodes. We applied this technology to the dynamic analysis of hematopoietic tumor cells that represent a particular challenge for real-time imaging due to their dislodgement during image acquisition. The present study was designed to provide a comprehensive mechanistic rationale for accelerated cell-based assays on DEP chips using real-time labeling with cell permeability markers. In this context, we provide data on the complex behavior of viable vs dying cells in the DEP fields and probe the effects of DEP fields upon cell responses to anticancer drugs and overall bioassay performance. Results indicate that simple DEP cell immobilization technology can be readily applied for the dynamic analysis of investigational drugs in hematopoietic cancer cells. This ability is of particular importance in studying the outcome of patient derived cancer cells, when exposed to therapeutic drugs, as these cells are often rare and difficult to collect, purify and immobilize.     

Anthropogenic and natural radionuclides in caribou and muskoxen in the western Alaskan Arctic and marine fish in the Aleutian Islands in the first half of 2000s

A number of caribou and muskoxen samples from the western Alaskan Arctic and fish samples from the Aleutian Islands were collected between 1998 and 2006 and analyzed for anthropogenic (⁹⁰Sr and ¹³⁷Cs) and natural radionculides (⁴⁰ K, ²¹⁰Pb and ²²⁶Ra), as part of the radiological assessment for the regional subsistence hunting communities in the first half of 2000s. We examined the relationship between the activities of these nuclides with the size of the fish. In caribou samples, concentration of ⁹⁰Sr in muscle was below the detection limit of 0.14 Bq kg^− 1 and ¹³⁷Cs concentration in bones was below the detection limit of 0.15 Bq kg^− 1.¹³⁷Cs activity varied over an order of magnitude in caribou muscle samples with an average value of 2.5 Bq/kg wet wt. Average ¹³⁷Cs activity in muskoxen muscle was found to be 9.7 Bq/kg wet wt. However, there were a little variation (less than 60%) in ²¹⁰Pb, ⁴⁰ K, and ²²⁶Ra in both muscle and bone of both caribou and muskoxen. The activities of total ²¹⁰Pb in caribou and muskox bones were found to be 1-2 orders of magnitude higher than that of parent-supported ²¹⁰Pb indicating the potential for dating of bones of terrestrial mammals (time elapsed since the death of the animal) based on the excess ²¹⁰Pb method exists. In fish muscle samples, ¹³⁷Cs activity varied from below detection limit to 154 mBq/kg wet wt. and its content increased with the size of the fish due to its transfer through the food chain. Among the seven fish species investigated, ²¹⁰Pb activities varied almost an order of magnitude; however, ⁴⁰K and ²²⁶Ra activities varied less than a factor of two. Total annual effective dose due to ⁹⁰Sr and ¹³⁷Cs from the ingestion of those terrestrial and marine meats was estimated to be negligible (ca. 9 μSV/a) compared to the natural radionuclides present thus posing negligible radiological threat to humans.     

A lead isotopic study of the human bioaccessibility of lead in urban soils from Glasgow, Scotland

The human bioaccessibility of lead (Pb) in Pb-contaminated soils from the Glasgow area was determined by the Unified Bioaccessibility Research Group of Europe (BARGE) Method (UBM), an in vitro physiologically based extraction scheme that mimics the chemical environment of the human gastrointestinal system and contains both stomach and intestine compartments. For 27 soils ranging in total Pb concentration from 126 to 2160 mg kg^− 1 (median 539 mg kg^− 1), bioaccessibility as determined by the ‘stomach’ simulation (pH ~ 1.5) was 46-1580 mg kg^− 1, equivalent to 23-77% (mean 52%) of soil total Pb concentration. The corresponding bioaccessibility data for the ‘stomach + intestine’ simulation (pH ~ 6.3) were 6-623 mg kg^− 1 and 2-42% (mean 22%) of soil Pb concentration. The soil ²⁰⁶Pb/²⁰⁷Pb ratios ranged from 1.057 to 1.175. Three-isotope plots of ²⁰⁸Pb/²⁰⁶Pb against ²⁰⁶Pb/²⁰⁷Pb demonstrated that ²⁰⁶Pb/²⁰⁷Pb ratios were intermediate between values for source end-member extremes of imported Australian Pb ore (1.04) - used in the manufacture of alkyl Pb compounds (1.06-1.10) formerly added to petrol - and indigenous Pb ores/coal (1.17-1.19). The ²⁰⁶Pb/²⁰⁷Pb ratios of the UBM ‘stomach’ extracts were similar (< 0.01 difference) to those of the soil for 26 of the 27 samples (r = 0.993, p < 0.001) and lower in 24 of them. A slight preference for lower ²⁰⁶Pb/²⁰⁷Pb ratio was discernible in the UBM. However, the source of Pb appeared to be less important in determining the extent of UBM-bioaccessible Pb than the overall soil total Pb concentration and the soil phases with which the Pb was associated. The significant phases identified in a subset of samples were carbonates, manganese oxides, iron-aluminium oxyhydroxides and clays.     

Lubricant‐Infused Nanoparticulate Coatings Assembled by Layer‐by‐Layer Deposition

Omniphobic coatings are designed to repel a wide range of liquids without leaving stains on the surface. A practical coating should exhibit stable repellency, show no interference with color or transparency of the underlying substrate and, ideally, be deposited in a simple process on arbitrarily shaped surfaces. We use layer‐by‐layer (LbL) deposition of negatively charged silica nanoparticles and positively charged polyelectrolytes to create nanoscale surface structures that are further surface‐functionalized with fluorinated silanes and infiltrated with fluorinated oil, forming a smooth, highly repellent coating on surfaces of different materials and shapes. We show that four or more LbL cycles introduce sufficient surface roughness to effectively immobilize the lubricant into the nanoporous coating and provide a stable liquid interface that repels water, low‐surface‐tension liquids and complex fluids. The absence of hierarchical structures and the small size of the silica nanoparticles enables complete transparency of the coating, with light transmittance exceeding that of normal glass. The coating is mechanically robust, maintains its repellency after exposure to continuous flow for several days and prevents adsorption of streptavidin as a model protein. The LbL process is conceptually simple, of low cost, environmentally benign, scalable, automatable and therefore may present an efficient synthetic route to non‐fouling materials.     

Bioinspired Scaffolds with Varying Pore Architectures and Mechanical Properties

Scaffolds with potential biological applications having a variety of microstructural and mechanical properties can be fabricated by freezing colloidal solutions into porous solids. In this work, the structural and mechanical properties of TiO₂ freeze cast with different soluble additives, including polyethylene glycol, NaOH or HCl, and isopropanol alcohol, are characterized to determine the effects of slurry viscosity, pH, and alcohol concentration on the freezing process. TiO₂ powders mixed with water and these different additives are directionally frozen in a mold, then sublimated and sintered to create the porous scaffolds. The different scaffolds are characterized to compare the compressive strength, modulus, porosity, and pore morphology. For all scaffolds, the overall porosity remains constant (80–85%). By changing the concentration of each additive, the lamellar thickness, pore area, and aspect ratio vary significantly, showing inverse relationships to both the compressive strength and modulus. The strength is predicted from the pore aspect ratio of the scaffolds when subjected to compressive loading with the primary failure mode identified as Euler buckling. TiO₂ scaffolds freeze cast with different soluble additives are suitable for biomedical applications, such as bone replacements, requiring high porosity and specific pore morphologies.     

Influence of ionic and nonionic surfactants on analytical parameters of ion-selective electrodes based on chelating active substances

The effects of the cationic (tetrabutylammonium chloride, TBC), anionic (sodium dodecyl sulfate, SDS) and nonionic (TRITON X-100) surfactants on the potentiometric properties of zinc- and cadmium-selective electrodes (ISEs) were investigated. The studies were carried out with plasticized PVC membranes doped with several new acidic chelating ionophores. The electrode basic analytical parameters, such as measurement range, slope characteristics, detection limit, response time and selectivity coefficients in relation to some inorganic cations in the presence and absence of surfactants, were investigated. As follows from the studies, the presence of surfactants in the sample is responsible first of all for the increase in response time and in detection limit, and a decrease in the characteristic slope as well as reduction of electrode selectivity.