Novel polymeric biomaterial poly(butyl-2-cyanoacrylate) nanowires: synthesis, characterization and formation mechanism.

Poly(butyl-2-cyanoacrylate) (PBCA) nanoparticles have been widely elaborated for nearly half a century. However, PBCA nanowires (PNWs) were seldom investigated. Here, new polymeric biomaterial PNWs were prepared via emulsion polymerization based on the sodium dodecyl sulfate (SDS)-assisted emulsion process. Results indicated that SDS micelles and PBCA polymer can develop surfactant-polymer complexes by self-assembly at room temperature. SDS concentration was confirmed to be the critical parameter for the association of the surfactant and the polymer. With the addition of SDS (0-40 mM), the interaction between SDS and PBCA led to a series of transitions from nanoparticles to nanowires. These morphology transitions were triggered by changing the electrostatic repulsion in the SDS-PBCA system, confirmed by the variety of zeta potential with increasing molar contents of SDS. To overcome the electrostatic repulsion, the complexes underwent transitions from spherical, worm-like (short-cylindrical), to elongated-cylindrical form. Finally, associated with the results from scanning / transmission electron microscopy (SEM / TEM), the elongated-cylindrical PNWs acquired at 20 mM of SDS were chosen to execute cell viability assay, which showed that they had no toxicity but with good-biocompatibility at the doses ≤ 50 µg/ml. These results indicate that the PNWs prepared by this facile-green and low-toxic strategy can potentially work as promising biomaterials in the biomedicine field.

Flexible elastomer patch with vertical silicon nanoneedles for intracellular and intratissue nanoinjection of biomolecules.

Vertically ordered arrays of silicon nanoneedles (Si NNs), due to their nanoscale dimension and low cytotoxicity, could enable minimally invasive nanoinjection of biomolecules into living biological systems such as cells and tissues. Although production of these Si NNs on a bulk Si wafer has been achieved through standard nanofabrication technology, there exists a large mismatch at the interface between the rigid, flat, and opaque Si wafer and soft, curvilinear, and optically transparent biological systems. Here, we report a unique methodology that is capable of constructing vertically ordered Si NNs on a thin layer of elastomer patch to flexibly and transparently interface with biological systems. The resulting outcome provides important capabilities to form a mechanically elastic interface between Si NNs and biological systems, and simultaneously enables direct imaging of their real-time interactions under the transparent condition. We demonstrate its utility in intracellular, intradermal, and intramuscular nanoinjection of biomolecules into various kinds of biological cells and tissues at their length scales.

Induction of protein citrullination and auto-antibodies production in murine exposed to nickel nanomaterials.

Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity.

Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51.

The possibility that traumatic brain injury (TBI) occurring in a cold environment exacerbates brain pathology and oxidative stress was examined in our rat model. TBI was inflicted by making a longitudinal incision into the right parietal cerebral cortex (2 mm deep and 4 mm long) in cold-acclimatized rats (5 °C for 3 h daily for 5 weeks) or animals at room temperature under Equithesin anesthesia. TBI in cold-exposed rats exhibited pronounced increase in brain lucigenin (LCG), luminol (LUM), and malondialdehyde (MDA) and marked pronounced decrease in glutathione (GTH) as compared to identical TBI at room temperature. The magnitude and intensity of BBB breakdown to radioiodine and Evans blue albumin, edema formation, and neuronal injuries were also exacerbated in cold-exposed rats after injury as compared to room temperature. Nanowired delivery of H-290/51 (50 mg/kg) 6 and 8 h after injury in cold-exposed group significantly thwarted brain pathology and oxidative stress whereas normal delivery of H-290/51 was neuroprotective after TBI at room temperature only. These observations are the first to demonstrate that (i) cold aggravates the pathophysiology of TBI possibly due to an enhanced production of oxidative stress, (ii) and in such conditions, nanodelivery of antioxidant compound has superior neuroprotective effects, not reported earlier.

TiO2-Nanowired Delivery of DL-3-n-butylphthalide (DL-NBP) Attenuates Blood-Brain Barrier Disruption, Brain Edema Formation, and Neuronal Damages Following Concussive Head Injury.

DL-3-n-butylphthalide (DL-NBP) is one of the constituents of Chinese celery extract that is used to treat stroke, dementia, and ischemic diseases. However, its role in traumatic brain injury is less well known. In this investigation, neuroprotective effects of DL-NBP in concussive head injury (CHI) on brain pathology were explored in a rat model. CHI was inflicted in anesthetized rats by dropping a weight of 114.6 g from a height of 20 cm through a guide tube on the exposed right parietal bone inducing an impact of 0.224 N and allowed them to survive 4 to 24 h after the primary insult. DL-NBP was administered (40 or 60 mg/kg, i.p.) 2 and 4 h after injury in 8-h survival group and 8 and 12 h after trauma in 24-h survival group. In addition, TiO2-nanowired delivery of DL-NBP (20 or 40 mg/kg, i.p.) in 8 and 24 h CHI rats was also examined. Untreated CHI showed a progressive increase in blood-brain barrier (BBB) breakdown to Evans blue albumin (EBA) and radioiodine ([131]-I), edema formation, and neuronal injuries. The magnitude and intensity of these pathological changes were most marked in the left hemisphere. Treatment with DL-NBP significantly reduced brain pathology in CHI following 8 to 12 h at 40-mg dose. However, 60-mg dose is needed to thwart brain pathology at 24 h following CHI. On the other hand, TiO2-DL-NBP was effective in reducing brain damage up to 8 or 12 h using a 20-mg dose and only 40-mg dose was needed for neuroprotection in CHI at 24 h. These observations are the first to suggest that (i) DL-NBP is quite effective in reducing brain pathology and (ii) nanodelivery of DL-NBP has far more superior effects in CHI, not reported earlier.

Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease.

Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (AßP), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of AßP (1-40) in the left lateral ventricle (250 ng/10 µl, once daily) for 4 weeks. After 30 days, the rats were examined for NPL and AßP concentrations in the brain and related pathology. Co-administration of TiO2-nanowired MSCs (106 cells) with 2.5 ml/kg CBL (i.v.) once daily for 1 week after 2 weeks of AßP infusion significantly increased the NPL in the hippocampus (400 pg/g) from the untreated control group (120 pg/g; control 420 ± 8 pg/g brain) along with a significant decrease in the AßP deposition (45 pg/g from untreated control 75 pg/g; saline control 40 ± 4 pg/g). Interestingly, these changes were much less evident when the MSCs or CBL treatment was given alone. Neuronal damages, gliosis, and myelin vesiculation were also markedly reduced by the combined treatment of TiO2, MSCs, and CBL in AD. These observations are the first to show that co-administration of TiO2-nanowired CBL and MSCs has superior neuroprotective effects in AD probably due to increasing the brain NPL level effectively, not reported earlier.

Repeated Forced Swim Exacerbates Methamphetamine-Induced Neurotoxicity: Neuroprotective Effects of Nanowired Delivery of 5-HT3-Receptor Antagonist Ondansetron.

The possibility that stress associated with chronic forced swim (FS) may exacerbate methamphetamine (METH) neurotoxicity was examined in a rat model. Rats were subjected to FS in a pool (30 °C) for 15 min daily for 8 days. Control rats were kept at room temperature. METH was administered (9 mg/kg, s.c.) in both control and FS rats and allowed to survive 4 h after the drug injection. METH in FS rats exacerbated BBB breakdown to Evans blue albumin (EBA) by 150 to 220% and [131]-Iodine by 250 to 380% as compared to naive rats after METH. The METH-induced BBB leakage was most pronounced in the cerebral cortex followed by the hippocampus, cerebellum, thalamus, and hypothalamus in both FS and naive rats. The regional BBB changes were associated with a reduction in the local cerebral blood flow (CBF). Brain edema was also higher by 2 to 4% in FS rats after METH than in naive animals. Neuronal and glial cell injuries were aggravated by threefold to fivefold after METH in FS than the control group. Pretreatment with ondansetron (1 mg/kg, i.p.) 30 min before METH injection in naive rats reduced the brain pathology and improved the CBF. However, TiO2-nanowired delivery of ondansetron (1 mg/kg, i.p.) was needed to reduce METH-induced brain damage, BBB leakage, reduction in CBF, and edema formation in FS. Taken together, these observations are the first to show that METH exacerbates BBB breakdown leading to neurotoxicity in FS animals. This effect of METH-induced BBB breakdown and brain pathology in naive and FS rats is attenuated by ondansetron treatment indicating an involvement of 5-HT3 receptors, not reported earlier.

Injectable Polymeric Cytokine-Binding Nanowires Are Effective Tissue-Specific Immunomodulators.

Injectable nanomaterials that interact with the host immune system without surgical intervention present spatially anchored complements to cell transplantation and could offer improved pharmacokinetics compared to systemic cytokine therapy. Here we demonstrate fabrication of high aspect ratio polycaprolactone nanowires coupled with cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. These structures are fabricated using a nanotemplating technique that allows for tunability of particle dimensions and utilize a straightforward maleimide conjugation chemistry to allow site-specific coupling to proteins. Nanowires are well tolerated in vivo and incite minimal inflammatory infiltrate. Nanowires conjugated with antibodies were designed to capture and potentiate endogenous interleukin-2 (IL-2), an important leukocyte activating cytokine. Together these nanowire-antibody matrices were capable of localizing endogenous IL-2 in the skin and activated targeted specific natural killer and T cell subsets, demonstrating both tissue- and cell-specific immune activation. These self-assembling nanowire matrices show promise as scaffolds to present engineered, local receptor-ligand interactions for cytokine-mediated disease.

Histaminergic Receptors Modulate Spinal Cord Injury-Induced Neuronal Nitric Oxide Synthase Upregulation and Cord Pathology: New Roles of Nanowired Drug Delivery for Neuroprotection.

The possibility that histamine influences the spinal cord pathophysiology following trauma through specific receptor-mediated upregulation of neuronal nitric oxide synthase (nNOS) was examined in a rat model. A focal spinal cord injury (SCI) was inflicted by a longitudinal incision into the right dorsal horn of the T10-11 segments. The animals were allowed to survive 5h. The SCI significantly induced breakdown of the blood-spinal cord barrier to protein tracers, reduced the spinal cord blood flow at 5h, and increased the edema formation and massive upregulation of nNOS expression. Pretreatment with histamine H1 receptor antagonist mepyramine (1mg, 5mg, and 10mg/kg, i.p., 30min before injury) failed to attenuate nNOS expression and spinal cord pathology following SCI. On the other hand, blockade of histamine H2 receptors with cimetidine or ranitidine (1mg, 5mg, or 10mg/kg) significantly reduced these early pathophysiological events and attenuated nNOS expression in a dose-dependent manner. Interestingly, TiO2-naowire delivery of cimetidine or ranitidine (5mg doses) exerted superior neuroprotective effects on SCI-induced nNOS expression and cord pathology. It appears that effects of ranitidine were far superior than cimetidine at identical doses in SCI. On the other hand, pretreatment with histamine H3 receptor agonist α-methylhistamine (1mg, 2mg, or 5mg/kg, i.p.) that inhibits histamine synthesis and release in the central nervous system thwarted the spinal cord pathophysiology and nNOS expression when used in lower doses. Interestingly, histamine H3 receptor antagonist thioperamide (1mg, 2mg, or 5mg/kg, i.p.) exacerbated nNOS expression and cord pathology after SCI. These novel observations suggest that blockade of histamine H2 receptors or stimulation of histamine H3 receptors attenuates nNOS expression and induces neuroprotection in SCI. Taken together, our results are the first to demonstrate that histamine-induced pathophysiology of SCI is mediated via nNOS expression involving specific histamine receptors.

Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats.

There is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 µm) and long (L-AgNWs; 10 µm) nanowires instilled into the lungs of Sprague-Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health.

Radio frequency-mediated local thermotherapy for destruction of pancreatic tumors using Ni-Au core-shell nanowires.

We present a novel method of radio frequency (RF)-mediated thermotherapy in tumors by remotely heating nickel (Ni)-gold (Au) core-shell nanowires (CSNWs). Ectopic pancreatic tumors were developed in nude mice to evaluate the thermotherapeutic effects on tumor progression. Tumor ablation was produced by RF-mediated thermotherapy via activation of the paramagnetic properties of the Ni-Au CSNWs. Histopathology demonstrated that heat generated by RF irradiation caused significant cellular death with pyknotic nuclei and nuclear fragmentation dispersed throughout the tumors. These preliminary results suggest that thermotherapy ablation induced via RF activation of nanowires provides a potential alternative therapy for cancer treatment.

Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death.

Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

Impact of degradable nanowires on long-term brain tissue responses.

BACKGROUND: A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. Nanostructured interfaces could improve the integration and communication stability, partly through the reduction of the cell-to-electrode distance. However, the safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses. RESULTS: The tissue response after injection of degradable silicon oxide (SiOx)-coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP nanowires into the rat striatum was compared. One year after nanowire injection, no significant difference in microglial or astrocytic response, as measured by staining for ED1 and glial fibrillary acidic protein, respectively, or in neuronal density, as measured by staining for NeuN, was found between degradable and biostable nanowires. Of the cells investigated, only microglia cells had engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in aggregated hypertrophic ED1-positive cells, possibly microglial cells that have fused to create multinucleated giant cells. Occasionally, degradable nanowires with an apparently intact shape were found inside single, small ED1-positive cells. The biostable nanowires were found intact in microglia cells of both phenotypes described. CONCLUSION: The present study shows that the degradable nanowires remain at least partly in the brain over long time periods, i.e. 1 year; however, no obvious bio-safety issues for this degradable nanomaterial could be detected.

Spontaneous Internalization of Cell Penetrating Peptide-Modified Nanowires into Primary Neurons.

Semiconductor nanowire (NW) devices that can address intracellular electrophysiological events with high sensitivity and spatial resolution are emerging as key tools in nanobioelectronics. Intracellular delivery of NWs without compromising cellular integrity and metabolic activity has, however, proven difficult without external mechanical forces or electrical pulses. Here, we introduce a biomimetic approach in which a cell penetrating peptide, the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1, is linked to the surface of Si NWs to facilitate spontaneous internalization of NWs into primary neuronal cells. Confocal microscopy imaging studies at fixed time points demonstrate that TAT-conjugated NWs (TAT-NWs) are fully internalized into mouse hippocampal neurons, and quantitative image analyses reveal an ca. 15% internalization efficiency. In addition, live cell dynamic imaging of NW internalization shows that NW penetration begins within 10-20 min after binding to the membrane and that NWs become fully internalized within 30-40 min. The generality of cell penetrating peptide modification method is further demonstrated by internalization of TAT-NWs into primary dorsal root ganglion (DRG) neurons.

Remote-controlled eradication of astrogliosis in spinal cord injury via electromagnetically-induced dexamethasone release from "smart" nanowires.

We describe a system to deliver drugs to selected tissues continuously, if required, for weeks. Drugs can be released remotely inside the small animals using pre-implanted, novel vertically aligned electromagnetically-sensitive polypyrrole nanowires (PpyNWs). Approximately 1-2mm(2) dexamethasone (DEX) doped PpyNWs was lifted on a single drop of sterile water by surface tension, and deposited onto a spinal cord lesion in glial fibrillary acidic protein-luc transgenic mice (GFAP-luc mice). Overexpression of GFAP is an indicator of astrogliosis/neuroinflammation in CNS injury. The corticosteroid DEX, a powerful ameliorator of inflammation, was released from the polymer by external application of an electromagnetic field for 2h/day for a week. The GFAP signal, revealed by bioluminescent imaging in the living animal, was significantly reduced in treated animals. At 1week, GFAP was at the edge of detection, and in some experimental animals, completely eradicated. We conclude that the administration of drugs can be controlled locally and non-invasively, opening the door to many other known therapies, such as the cases that dexamethasone cannot be safely applied systemically in large concentrations.

Silicon nanowire-induced maturation of cardiomyocytes derived from human induced pluripotent stem cells.

The current inability to derive mature cardiomyocytes from human pluripotent stem cells has been the limiting step for transitioning this powerful technology into clinical therapies. To address this, scaffold-based tissue engineering approaches have been utilized to mimic heart development in vitro and promote maturation of cardiomyocytes derived from human pluripotent stem cells. While scaffolds can provide 3D microenvironments, current scaffolds lack the matched physical/chemical/biological properties of native extracellular environments. On the other hand, scaffold-free, 3D cardiac spheroids (i.e., spherical-shaped microtissues) prepared by seeding cardiomyocytes into agarose microwells were shown to improve cardiac functions. However, cardiomyocytes within the spheroids could not assemble in a controlled manner and led to compromised, unsynchronized contractions. Here, we show, for the first time, that incorporation of a trace amount (i.e., ∼0.004% w/v) of electrically conductive silicon nanowires (e-SiNWs) in otherwise scaffold-free cardiac spheroids can form an electrically conductive network, leading to synchronized and significantly enhanced contraction (i.e., >55% increase in average contraction amplitude), resulting in significantly more advanced cellular structural and contractile maturation.

Short versus long silver nanowires: a comparison of in vivo pulmonary effects post instillation.

BACKGROUND: Silver nanowires (Ag NWs) are increasingly being used to produce touchscreens for smart phones and computers. When applied in a thin film over a plastic substrate, Ag NWs create a transparent, highly-conductive network of fibers enabling the touch interface between consumers and their electronics. Large-scale application methods utilize techniques whereby Ag NW suspensions are deposited onto substrates via droplets. Aerosolized droplets increase risk of occupational Ag NW exposure. Currently, there are few published studies on Ag NW exposure-related health effects. Concerns have risen about the potential for greater toxicity from exposure to high-aspect ratio nanomaterials compared to their non-fibrous counterparts. This study examines whether Ag NWs of varying lengths affect biological responses and silver distribution within the lungs at different time-points. METHODS: Two different sizes of Ag NWs (2 µm [S-Ag NWs] and 20 µm [L-Ag NWs]) were tested. Male, Sprague-Dawley rats were intratracheally instilled with Ag NWs (0, 0.1, 0.5, or 1.0 mg/kg). Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, and 21 days post exposure for analysis of BAL total cells, cell differentials, and total protein as well as tissue pathology and silver distribution. RESULTS AND CONCLUSIONS: The two highest doses produced significant increases in BAL endpoints. At Day 1, Ag NWs increased total cells, inflammatory polymorphonuclear cells (PMNs), and total protein. PMNs persisted for both Ag NW types at Day 7, though not significantly so, and by Day 21, PMNs appeared in line with sham control values. Striking histopathological features associated with Ag NWs included 1) a strong influx of eosinophils at Days 1 and 7; and 2) formation of Langhans and foreign body giant cells at Days 7 and 21. Epithelial sloughing in the terminal bronchioles (TB) and cellular exudate in alveolar regions were also common. By Day 21, Ag NWs were primarily enclosed in granulomas or surrounded by numerous macrophages in the TB-alveolar duct junction. These findings suggest short and long Ag NWs produce pulmonary toxicity; thus, further research into exposure-related health effects and possible exposure scenarios are necessary to ensure human safety as Ag NW demand increases.

Plasma membrane and actin cytoskeleton as synergistic barriers to nanowire cell penetration.

Nanowires are a rapidly emerging platform for manipulation of and material delivery directly into the cell cytosol. These high aspect ratio structures can breach the lipid membrane; however, the yield of penetrant structures is low, and the mechanism is largely unknown. In particular, some nanostructures appear to defeat the membrane transiently, while others can retain long-term access. Here, we examine if local dissolution of the lipid membrane, actin cytoskeleton, or both can enhance nanowire penetration. It is possible that, during cell contact, membrane rupture occurs; however, if the nanostructures do not penetrate the cytoskeleton, the membrane may reclose over a relatively short time frame. We show with quantitative analysis of the number of penetrating nanowires that the lipid bilayer and actin cytoskeleton are synergistic barriers to nanowire cell access, yet chemical poration through both is still insufficient to increase long-term access for adhered cells.

Dissolution of silver nanowires and nanospheres dictates their toxicity to Escherichia coli.

Silver nanoparticles are extensively used in antibacterial applications. However, the mechanisms of their antibacterial action are not yet fully explored. We studied the solubility-driven toxicity of 100 × 6100 nm (mean primary diameter × length) silver nanowires (NWs) to recombinant bioluminescent Escherichia coli as a target representative of enteric pathogens. The bacteria were exposed to silver nanostructures in water to exclude the speciation-driven alterations. Spherical silver nanoparticles (83 nm mean primary size) were used as a control for the effect of NPs shape. Toxicity of both Ag NWs and spheres to E. coli was observed at similar nominal concentrations: the 4h EC50 values, calculated on the basis of inhibition of bacterial bioluminescence, were 0.42 ± 0.06 and 0.68 ± 0.01 mg Ag/L, respectively. Dissolution and bioavailability of Ag from NWs and nanospheres, analyzed with AAS or Ag-sensor bacteria, respectively, suggested that the toxic effects were caused by solubilized Ag(+) ions. Moreover, the antibacterial activities of Ag NWs suspension and its ultracentrifuged particle-free supernatant were equal. The latter indicated that the toxic effects of ~80-100 nm Ag nanostructures to Escherichia coli were solely dependent on their dissolution and no shape-induced/related effects were observed. Yet, additional nanospecific effects could come into play in case of smaller nanosilver particles.

Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function.

Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clean-room staff fabricating and characterizing the nanowires are at risk of exposure, emphasizing the importance of investigating their possible toxicity. Here we investigated the effects of gallium phosphide nanowires on the fruit fly Drosophila melanogaster. Drosophila larvae and/or adults were exposed to gallium phosphide nanowires by ingestion with food. The toxicity and tissue interaction of the nanowires was evaluated by investigating tissue distribution, activation of immune response, genome-wide gene expression, life span, fecundity and somatic mutation rates. Our results show that gallium phosphide nanowires applied through the diet are not taken up into Drosophila tissues, do not elicit a measurable immune response or changes in genome-wide gene expression and do not significantly affect life span or somatic mutation rate.