A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.     

Knowledge-based hand tool selection in concurrent design of mechanical systems

Selection of hand tools for cost-effective assembly and maintenance of a mechanical system has a significant impact on its life-cycle cost. A knowledge-based automated procedure for the selection of hand tools needed to efficiently carry out fastening operations in a mechanical assembly is presented. The objective is to select a tool that is applicable to a particular fastening operation, minimizes time and cost of the fastening operation, and satisfies accessibility requirements, and to provide design assistance to the design engineer. The role of the tool selection procedure in the concurrent design of mechanical systems is described.     

Biodegradation of single-walled carbon nanotubes through enzymatic catalysis

We show here the biodegradation of single-walled carbon nanotubes through natural, enzymatic catalysis. By incubating nanotubes with a natural horseradish peroxidase (HRP) and low concentrations of H2O2 (approximately 40 microM) at 4 degrees C over 12 weeks under static conditions, we show the increased degradation of nanotube structure. This reaction was monitored via multiple characterization methods, including transmission electron microscopy (TEM), dynamic light scattering (DLS), gel electrophoresis, mass spectrometry, and ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy. These results mark a promising possibility for carbon nanotubes to be degraded by HRP in environmentally relevant settings. This is also tempting for future studies involving biotechnological and natural (plant peroxidases) ways for degradation of carbon nanotubes in the environment.     

An integrated methodology for assessing the impact of food matrix and gastrointestinal effects on the biokinetics and cellular toxicity of ingested engineered nanomaterials

Background

Engineered nanomaterials (ENMs) are increasingly added to foods to improve their quality, sensory appeal, safety and shelf-life. Human exposure to these ingested ENMs (iENMS) is inevitable, yet little is known of their hazards. To assess potential hazards, efficient in vitro methodologies are needed to evaluate particle biokinetics and toxicity. These methodologies must account for interactions and transformations of iENMs in foods (food matrix effect) and in the gastrointestinal tract (GIT) that are likely to determine nano-biointeractions. Here we report the development and application of an integrated methodology consisting of three interconnected stages: 1) assessment of iENM-food interactions (food matrix effect) using model foods; 2) assessment of gastrointestinal transformations of the nano-enabled model foods using a three-stage GIT simulator; 3) assessment of iENMs biokinetics and cellular toxicity after exposure to simulated GIT conditions using a triculture cell model. As a case study, a model food (corn oil-in-water emulsion) was infused with Fe₂O₃ (Iron(III) oxide or ferric oxide) ENMs and processed using this three-stage integrated platform to study the impact of food matrix and GIT effects on nanoparticle biokinetics and cytotoxicity .

Methods

A corn oil in phosphate buffer emulsion was prepared using a high speed blender and high pressure homogenizer. Iron oxide ENM was dispersed in water by sonication and combined with the food model. The resulting nano-enabled food was passed through a three stage (mouth, stomach and small intestine) GIT simulator. Size distributions of nano-enabled food model and digestae at each stage were analyzed by DLS and laser diffraction. TEM and confocal imaging were used to assess morphology of digestae at each phase. Dissolution of Fe2O3 ENM along the GIT was assessed by ICP-MS analysis of supernatants and pellets following centrifugation of digestae. An in vitro transwell triculture epithelial model was used to assess biokinetics and toxicity of ingested Fe₂O₃ ENM. Translocation of Fe₂O₃ ENM was determined by ICP-MS analysis of cell lysates and basolateral compartment fluid over time.

Results

It was demonstrated that the interactions of iENMs with food and GIT components influenced nanoparticle fate and transport, biokinetics and toxicological profile. Large differences in particle size, charge, and morphology were observed in the model food with and without Fe₂O₃ and among digestae from different stages of the simulated GIT (mouth, stomach, and small intestine). Immunoflorescence and TEM imaging of the cell culture model revealed markers and morphology of small intestinal epithelium including enterocytes, goblet cells and M cells. Fe₂O₃ was not toxic at concentrations tested in the digesta. In biokinetics studies, translocation of Fe₂O₃ after 4 h was <1% and ~2% for digesta with and without serum, respectively, suggesting that use of serum proteins alters iENMs biokinetics and raises concerns about commonly-used approaches that neglect iENM – food-GIT interactions or dilute digestae in serum-containing media.

Conclusions

We present a simple integrated methodology for studying the biokinetics and toxicology of iENMs, which takes into consideration nanoparticle-food-GIT interactions. The importance of food matrix and GIT effects on biointeractions was demonstrated, as well as the incorporation of these critical factors into a cellular toxicity screening model. Standardized food models still need to be developed and used to assess the effect of the food matrix effects on the fate and bioactivity of iENMs since commercial foods vary considerably in their compositions and structures.

     

Protein corona: implications for nanoparticle interactions with pulmonary cells

Background

We previously showed that cerium oxide (CeO₂), barium sulfate (BaSO₄) 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

CeO₂, silica-coated CeO₂, BaSO₄, and ZnO NPs were incubated in rat lung lining fluid in vitro. Then, gel electrophoresis followed by quantitative mass spectrometry was used to characterize the adsorbed proteins stripped from these NPs. We also measured uptake of instilled NPs by alveolar macrophages (AMs) in rat lungs using electron microscopy. Finally, we tested whether coating of gold NPs with albumin would alter their lung clearance in rats.

Results

We found that the amounts of nine proteins in the coronas formed on the four NPs varied significantly. The amounts of albumin, transferrin and α-1 antitrypsin were greater in the coronas of BaSO₄ and ZnO than that of the two CeO₂ NPs. The uptake of BaSO₄ in AMs was less than CeO₂ and silica-coated CeO₂ NPs. No identifiable ZnO NPs were observed in AMs. Gold NPs coated with albumin or citrate instilled into the lungs of rats acquired the similar protein coronas and were cleared from the lungs to the same extent.

Conclusions

We show that different NPs variably adsorb proteins from the lung lining fluid. The amount of albumin in the NP corona varies as does NP uptake by AMs. However, albumin coating does not affect the translocation of gold NPs across the air-blood barrier. A more extensive database of corona composition of a diverse NP library will develop a platform to help predict the effects and biokinetics of inhaled NPs.

     

Sampling from discrete Gaussians for lattice-based cryptography on a constrained device

Modern lattice-based public-key cryptosystems require sampling from discrete Gaussian (normal) distributions. The paper surveys algorithms to implement such sampling efficiently, with particular focus on the case of constrained devices with small on-board storage and without access to large numbers of external random bits. We review lattice encryption schemes and signature schemes and their requirements for sampling from discrete Gaussians. Finally, we make some remarks on challenges and potential solutions for practical lattice-based cryptography.     

Mixing enhancement using chevron nozzle: studies on free jets and confined jets

This paper reports an experimental study focused on the impact of chevrons (serrations on the trailing edge of the nozzle) on the mixing process of an incompressible jet issuing from a convergent nozzle. The study also explores enhancement of the mixing performance by a novel approach to geometry modification. Profiles of mean velocity were used to characterize the extent of mixing. For a comparative assessment, studies were carried out with a base line circular nozzle, a conventional chevron nozzle and an improvised tabbed chevron nozzle. Flow visualization studies were carried out for jets issuing from chevron nozzles and the results corroborate well with quantitative measurements. The impact of confinement on mixing of jets issuing from chevron nozzles is also studied. The results show that the proposed geometry modification can significantly improve the rate of mixing in the range of Reynolds numbers considered in the study. In confined jets, presence of chevrons was found to accelerate the process of jet break-down.