Pulmonary fate and consequences of transferrin-functionalized gold nanoparticles.

Surface functionalization of nanoparticles (NPs) may alter their biological interactions such as uptake by alveolar macrophages (AMs). Pulmonary delivery of gold NPs (Au NPs) has theranostic potential due to their optoelectronic properties, minimal alveoli to blood translocation, and possibility of specific cell targeting. Here, we examined whether coating Au NPs with transferrin alters their protein corona, uptake by macrophages, and pulmonary translocation.

Effects of Ingested Nanomaterials on Tissue Distribution of Co-ingested Zinc and Iron in Normal and Zinc-Deficient Mice.

Cellulose nanofibers (CNF) reduced serum triglyceride levels in rats when co-administered with heavy cream by gavage. Do CNF and other nanomaterials (NMs) alter the tissue distribution and retention of co-administered metal ions? We evaluated whether 5 different NMs affected tissue distribution of co-ingested Zn and Fe in zinc-replete versus zinc-deficient mice. Male C57BL/6J mice were fed either zinc-replete or zinc-deficient diets for 3 weeks, followed by gavage with NM suspensions in water containing both ZnCl and FeCl.

Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity.

Background: Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials.

Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques - A Review.

A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy.

Preserving Airway Smooth Muscle Contraction in Precision-Cut Lung Slices.

Precision-cut lung slices (PCLS) are ideal for measuring small airway contraction. However, these measurements are currently limited to acute exposure scenarios that typically last a few minutes to a few hours. Using an insulin-supplemented culture medium, we prolong the small airway contractility in mouse PCLS for up to two weeks.

Toxicological effects of ingested nanocellulose in in vitro intestinal epithelium and in vivo rat models.

Cellulose is widely used as a thickener and filler in foods and drugs. It has been designated "generally regarded as safe" (GRAS). Nanocellulose (NC) has many additional potential applications designed to improve food quality and safety, but has not yet been designated as GRAS.

Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.

Do immature lungs have air-blood barriers that are more permeable to inhaled nanoparticles than those of fully developed mature lungs? Data supporting this notion and explaining the underlying mechanisms do not exist as far as we know. Using a rat model of postnatal lung development, here the data exactly supporting this notion, that is, significantly more gold nanoparticles (NPs) cross from the air space of the lungs to the rest of the body in neonates than in adults, are presented. Moreover, in neonates the translocation of gold NPs is not size dependent, whereas in adult animals smaller NPs cross the air-blood lung barrier much more efficiently than larger NPs.

Fate of Barium Sulfate Nanoparticles Deposited in the Lungs of Rats.

We have shown that barium [from BaSO nanoparticles (NPs)] was cleared from the lungs faster than other poorly soluble NPs and translocated mostly to bone. We now studied barium biokinetics in rats during Study 1: two-year inhalation exposure to 50 mg/m BaSO NP aerosols, and Study 2: single intratracheal (IT) instillation of increasing doses of BaSO NPs or BaCl. Study 1 showed that lung barium content measured by inductively coupled plasma mass spectrometry increased during 360 days of BaSO NP aerosol exposures.

Repeated pulmonary exposures to zinc ions enhance inflammatory responses to subsequent metal exposures.

Aim Of Study: Metal contaminants contribute to adverse human health effects via acute and chronic exposures. Acute metal exposures followed by prolonged secondary metal exposures may elicit exaggerated inflammatory responses in certain individuals. The aim of this study is to determine whether repeated pulmonary exposures to zinc chloride (ZnCl) alter subsequent responses to zinc or cerium exposures.

Nanoparticle Wettability Influences Nanoparticle-Phospholipid Interactions.

We explored the influence of nanoparticle (NP) surface charge and hydrophobicity on NP-biomolecule interactions by measuring the composition of adsorbed phospholipids on four NPs, namely, positively charged CeO and ZnO and negatively charged BaSO and silica-coated CeO after exposure to bronchoalveolar lavage fluid (BALf) obtained from rats, and to a mixture of neutral dipalmitoyl phosphatidylcholine (DPPC) and negatively charged dipalmitoyl phosphatidic acid (DPPA). The resulting NP-lipid interactions were examined by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). Our data show that the amount of adsorbed lipids on NPs after incubation in BALf and the DPPC/DPPA mixture was higher in CeO than in the other NPs, qualitatively consistent with their relative hydrophobicity.

Effects of a vinegar-based multi-micronutrient supplement in rats: a multi-pronged assessment of dietary impact.

We determined the effects of continuous access to drinking of water with a vinegar-based multi-micronutrient (VMm) supplement containing rice and fruit vinegars, vitamins, organic acids and sugars during gestation, lactation, and early adulthood in rats. Pregnant rats were provided with reverse-osmosis water or VMm water from the start of pregnancy through the time of weaning. Weaned pups consumed the same drinking water for 3-12 additional weeks.

Protein corona: implications for nanoparticle interactions with pulmonary cells.

Background: We previously showed that cerium oxide (CeO), barium sulfate (BaSO) and zinc oxide (ZnO) nanoparticles (NPs) exhibited different lung toxicity and pulmonary clearance in rats. We hypothesize that these NPs acquire coronas with different protein compositions that may influence their clearance from the lungs.

Methods: CeO, silica-coated CeO, BaSO, and ZnO NPs were incubated in rat lung lining fluid in vitro.

Biokinetics of Nanomaterials: the Role of Biopersistence.

Nanotechnology risk management strategies and environmental regulations continue to rely on hazard and exposure assessment protocols developed for bulk materials, including larger size particles, while commercial application of nanomaterials (NMs) increases. In order to support and corroborate risk assessment of NMs for workers, consumers, and the environment it is crucial to establish the impact of biopersistence of NMs at realistic doses. In the future, such data will allow a more refined future categorization of NMs.

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation.

Particles can be delivered to the respiratory tract of animals using various techniques. Inhalation mimics environmental exposure but requires large amounts of aerosolized NPs over a prolonged dosing time, varies in deposited dose among individual animals, and results in nasopharyngeal and fur particle deposition. Although less physiological, intratracheal (IT) instillation allows quick and precise dosing.

Repeated Mouse Lung Exposures to Stachybotrys chartarum Shift Immune Response from Type 1 to Type 2.

After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multiple-dosed mice.

Screening for Chemical Toxicity Using Cryopreserved Precision Cut Lung Slices.

To assess chemical toxicity, current high throughput screening (HTS) assays rely primarily on in vitro measurements using cultured cells. Responses frequently differ from in vivo results due to the lack of physical and humoral interactions provided by the extracellular matrix, cell-cell interactions, and other molecular components of the native organ. To more accurately reproduce organ complexity in HTS, we developed an organotypic assay using the cryopreserved precision cut lung slice (PCLS) from rats and mice.

Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation.

Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated (65)ZnO or silica-coated (65)ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for (65)Zn radioactivity.

Silica coating influences the corona and biokinetics of cerium oxide nanoparticles.

Background: The physicochemical properties of nanoparticles (NPs) influence their biological outcomes.

Methods: We assessed the effects of an amorphous silica coating on the pharmacokinetics and pulmonary effects of CeO2 NPs following intratracheal (IT) instillation, gavage and intravenous injection in rats. Uncoated and silica-coated CeO2 NPs were generated by flame spray pyrolysis and later neutron-activated.

Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function.

Background: Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration.

Environmental mold and mycotoxin exposures elicit specific cytokine and chemokine responses.

Background: Molds can cause respiratory symptoms and asthma. We sought to use isolated peripheral blood mononuclear cells (PBMCs) to understand changes in cytokine and chemokine levels in response to mold and mycotoxin exposures and to link these levels with respiratory symptoms in humans. We did this by utilizing an ex vivo assay approach to differentiate mold-exposed patients and unexposed controls.

Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates.

Objectives: Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF), compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.

Research Design And Methods: Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry.