Magnetic characterization of superparamagnetic nanoparticles pulled through model membranes

Background

To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux densities, gradients, and nanoparticle properties were measured in order to quantify the magnetic force on the SPION in both an artificial cochlear round window membrane (RWM) model and the guinea pig RWM.

Methods

Three-dimensional maps were created for flux density and magnetic gradient produced by a 24-well casing of 4.1 kilo-Gauss neodymium-iron-boron (NdFeB) disc magnets. The casing was used to pull SPION through a three-layer cell culture RWM model. Similar maps were created for a 4 inch (10.16 cm) cube 48 MGOe NdFeB magnet used to pull polymeric-nanoparticles through the RWM of anesthetized guinea pigs. Other parameters needed to compute magnetic force were nanoparticle and polymer properties, including average radius, density, magnetic susceptibility, and volume fraction of magnetite.

Results

A minimum force of 5.04 × 10^-16 N was determined to adequately pull nanoparticles through the in-vitro model. For the guinea pig RWM, the magnetic force on the polymeric nanoparticles was 9.69 × 10^-20 N. Electron microscopy confirmed the movement of the particles through both RWM models.

Conclusion

As prospective carriers of therapeutic substances, polymers containing superparamagnetic iron oxide nanoparticles were succesfully pulled through the live RWM. The force required to achieve in vivo transport was significantly lower than that required to pull nanoparticles through the in-vitro RWM model. Indeed very little force was required to accomplish measurable delivery of polymeric-SPION composite nanoparticles across the RWM, suggesting that therapeutic delivery to the inner ear by SPION is feasible.

     

Temperature measurement on neurological pulse generators during MR scans

Background

Electromagnetic stimulation of the nervous system has the advantage of reduced discomfort in activating nerves. For brain structures stimulation, it has become a clinically accepted modality. Coil designs usually consider factors such as optimization of induced power, focussing, field shape etc. In this study we are attempting to find the effect of the coil contour shape on the electrical field distribution for magnetic stimulation.

Method and results

We use the maximum of the induced electric field stimulation in the region of interest as the optimization criterion. This choice required the application of the calculus of variation, with the contour perimeter taken as a pre-set condition. Four types of coils are studied and compared: circular, square, triangular and an 'optimally' shaped contour. The latter yields higher values of the induced electrical field in depths up to about 30 mm, but for depths around 100 mm, the circular shape has a slight advantage. The validity of the model results was checked by experimental measurements in a tank with saline solution, where differences of about 12% were found. In view the accuracy limitations of the computational and measurement methods used, such differences are considered acceptable.

Conclusion

We applied an optimization approach, using the calculus of variation, which allows to obtain a coil contour shape corresponding to a selected criterion. In this case, the optimal contour showed higher intensities for a longer line along the depth-axis. The method allows modifying the induced field structure and focussing the field to a selected zone or line.     

Single wall carbon nanotubes enter cells by endocytosis and not membrane penetration

Background

Quantitative analysis of nanoparticle uptake at the cellular level is critical to nanomedicine procedures. In particular, it is required for a realistic evaluation of their effects. Unfortunately, quantitative measurements of nanoparticle uptake still pose a formidable technical challenge. We present here a method to tackle this problem and analyze the number of metal nanoparticles present in different types of cells. The method relies on high-lateral-resolution (better than 30 nm) transmission x-ray microimages with both absorption contrast and phase contrast -- including two-dimensional (2D) projection images and three-dimensional (3D) tomographic reconstructions that directly show the nanoparticles.

Results

Practical tests were successfully conducted on bare and polyethylene glycol (PEG) coated gold nanoparticles obtained by x-ray irradiation. Using two different cell lines, EMT and HeLa, we obtained the number of nanoparticle clusters uptaken by each cell and the cluster size. Furthermore, the analysis revealed interesting differences between 2D and 3D cultured cells as well as between 2D and 3D data for the same 3D specimen.

Conclusions

We demonstrated the feasibility and effectiveness of our method, proving that it is accurate enough to measure the nanoparticle uptake differences between cells as well as the sizes of the formed nanoparticle clusters. The differences between 2D and 3D cultures and 2D and 3D images stress the importance of the 3D analysis which is made possible by our approach.     

Distinct biological effects of different nanoparticles commonly used in cosmetics and medicine coatings

Background

Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine. Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe) for use as a food additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms. Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their biological effects.

Results

We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often activated when the cell is under stress.

Conclusion

We suggest that these image-based assays provide a method of screening for the biological effects of similar compounds that is both efficient and sensitive as well as do not involve the use of animals.     

Nano-biolistics: a method of biolistic transfection of cells and tissues using a gene gun with novel nanometer-sized projectiles

Background

Biolistic transfection is proving an increasingly popular method of incorporating DNA or RNA into cells that are difficult to transfect using traditional methods. The technique routinely uses 'microparticles', which are ~1 μm diameter projectiles, fired into tissues using pressurised gas. These microparticles are efficient at delivering DNA into cells, but cannot efficiently transfect small cells and may cause significant tissue damage, thus limiting their potential usefulness. Here we describe the use of 40 nm diameter projectiles - nanoparticles - in biolistic transfections to determine if they are a suitable alternative to microparticles.

Results

Examination of transfection efficiencies in HEK293 cells, using a range of conditions including different DNA concentrations and different preparation procedures, reveals similar behaviour of microparticles and nanoparticles. The use of nanoparticles, however, resulted in ~30% fewer damaged HEK293 cells following transfection. Biolistic transfection of mouse ear tissue revealed similar depth penetration for the two types of particles, and also showed that < 10% of nuclei were damaged in nanoparticle-transfected samples, compared to > 20% in microparticle-transfected samples. Visualising details of small cellular structures was also considerably enhanced when using nanoparticles.

Conclusions

We conclude that nanoparticles are as efficient for biolistic transfection as microparticles, and are more appropriate for use in small cells, when examining cellular structures and/or where tissue damage is a problem.     

Rapid Pharmacokinetic and Biodistribution Studies Using Cholorotoxin-Conjugated Iron Oxide Nanoparticles: A Novel Non-Radioactive Method

Background

Recent advances in nanotechnology have led to the development of biocompatible nanoparticles for in vivo molecular imaging and targeted therapy. Many nanoparticles have undesirable tissue distribution or unacceptably low serum half-lives. Pharmacokinetic (PK) and biodistribution studies can help inform decisions determining particle size, coatings, or other features early in nanoparticle development. Unfortunately, these studies are rarely done in a timely fashion because many nanotechnology labs lack the resources and expertise to synthesize radioactive nanoparticles and evaluate them in mice.

Methodology/Principal Findings

To address this problem, we developed an economical, radioactivity-free method for assessing serum half-life and tissue distribution of nanoparticles in mice. Iron oxide nanoparticles coated with chitosan and polyethylene glycol that utilize chlorotoxin as a targeting molecule have a serum half-life of 7–8 hours and the particles remain stable for extended periods of time in physiologic fluids and in vivo. Nanoparticles preferentially distribute to spleen and liver, presumably due to reticuloendothelial uptake. Other organs have very low levels of nanoparticles, which is ideal for imaging most cancers in the future. No acute toxicity was attributed to the nanoparticles.

Conclusions/Significance

We report here a simple near-infrared fluorescence based methodology to assess PK properties of nanoparticles in order to integrate pharmacokinetic data into early nanoparticle design and synthesis. The nanoparticles tested demonstrate properties that are excellent for future clinical imaging strategies and potentially suitable for targeted therapy.     

Synthetic osteogenic extracellular matrix formed by coated silicon dioxide nanosprings

Background

Angiogenesis is widely investigated in conjunction with cancer development, in particular because of the possibility of early stage detection and of new therapeutic strategies. However, such studies are negatively affected by the limitations of imaging techniques in the detection of microscopic blood vessels (diameter 3-5 ??m) grown under angiogenic stress. We report that synchrotron-based X-ray imaging techniques with very high spatial resolution can overcome this obstacle, provided that suitable contrast agents are used.

Results

We tested different contrast agents based on gold nanoparticles (AuNPs) for the detection of cancer-related angiogenesis by synchrotron microradiology, microtomography and high resolution X-ray microscopy. Among them only bare-AuNPs in conjunction with heparin injection provided sufficient contrast to allow in vivo detection of small capillary species (the smallest measured lumen diameters were 3-5 ??m). The detected vessel density was 3-7 times higher than with other nanoparticles. We also found that bare-AuNPs with heparin allows detecting symptoms of local extravascular nanoparticle diffusion in tumor areas where capillary leakage appeared.

Conclusions

Although high-Z AuNPs are natural candidates as radiology contrast agents, their success is not guaranteed, in particular when targeting very small blood vessels in tumor-related angiography. We found that AuNPs injected with heparin produced the contrast level needed to reveal--for the first time by X-ray imaging--tumor microvessels with 3-5 ??m diameter as well as extravascular diffusion due to basal membrane defenestration. These results open the interesting possibility of functional imaging of the tumor microvasculature, of its development and organization, as well as of the effects of anti-angiogenic drugs.     

Low frequency magnetic emissions and resulting induced voltages in a pacemaker by iPod portable music players

Background

Recently, malfunctioning of a cardiac pacemaker electromagnetic, caused by electromagnetic interference (EMI) by fields emitted by personal portable music players was highly publicized around the world. A clinical study of one patient was performed and two types of interference were observed when the clinicians placed a pacemaker programming head and an iPod were placed adjacent to the patient's implanted pacemaker. The authors concluded that "Warning labels may be needed to avoid close contact between pacemakers and iPods". We performed an in-vitro study to evaluate these claims of EMI and present our findings of no-effects" in this paper.

Methods

We performed in-vitro evaluations of the low frequency magnetic field emissions from various models of the Apple Inc. iPod music player. We measured magnetic field emissions with a 3-coil sensor (diameter of 3.5 cm) placed within 1 cm of the surface of the player. Highly localized fields were observed (only existing in a one square cm area). We also measured the voltages induced inside an 'instrumented-can' pacemaker with two standard unipolar leads. Each iPod was placed in the air, 2.7 cm above the pacemaker case. The pacemaker case and leads were placed in a saline filled torso simulator per pacemaker electromagnetic compatibility standard ANSI/AAMI PC69:2000. Voltages inside the can were measured.

Results

Emissions were strongest (≈ 0.2 μT pp) near a few localized points on the cases of the two iPods with hard drives. Emissions consisted of 100 kHz sinusoidal signal with lower frequency (20 msec wide) pulsed amplitude modulation. Voltages induced in the iPods were below the noise level of our instruments (0.5 mV pp in the 0 - 1 kHz band or 2 mV pp in the 0 - 5 MHz bandwidth.

Conclusion

Our measurements of the magnitude and the spatial distribution of low frequency magnetic flux density emissions by 4 different models of iPod portable music players. Levels of less than 0.2 μT exist very close (1 cm) from the case. The measured voltages induced inside an 'instrumented-can' pacemaker were below the noise level of our instruments. Based on the observations of our in-vitro study we conclude that no interference effects can occur in pacemakers exposed to the iPod devices we tested.     

Porphyrin-magnetite nanoconjugates for biological imaging

Background  

The use of silica coated magnetic nanoparticles as contrast agents has resulted in the production of highly stable, non-toxic solutions that can be manipulated via an external magnetic field. As a result, the interaction of these nanocomposites with cells is of vital importance in understanding their behaviour and biocompatibility. Here we report the preparation, characterisation and potential application of new "two-in-one" magnetic fluorescent nanocomposites composed of silica-coated magnetite nanoparticles covalently linked to a porphyrin moiety.     

Peripheral nerve magnetic stimulation: influence of tissue non-homogeneity

Background

Peripheral nerves are situated in a highly non-homogeneous environment, including muscles, bones, blood vessels, etc. Time-varying magnetic field stimulation of the median and ulnar nerves in the carpal region is studied, with special consideration of the influence of non-homogeneities.

Methods

A detailed three-dimensional finite element model (FEM) of the anatomy of the wrist region was built to assess the induced currents distribution by external magnetic stimulation. The electromagnetic field distribution in the non-homogeneous domain was defined as an internal Dirichlet problem using the finite element method. The boundary conditions were obtained by analysis of the vector potential field excited by external current-driven coils.

Results

The results include evaluation and graphical representation of the induced current field distribution at various stimulation coil positions. Comparative study for the real non-homogeneous structure with anisotropic conductivities of the tissues and a mock homogeneous media is also presented. The possibility of achieving selective stimulation of either of the two nerves is assessed.

Conclusion

The model developed could be useful in theoretical prediction of the current distribution in the nerves during diagnostic stimulation and therapeutic procedures involving electromagnetic excitation. The errors in applying homogeneous domain modeling rather than real non-homogeneous biological structures are demonstrated. The practical implications of the applied approach are valid for any arbitrary weakly conductive medium.

     

A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles

Background

Particle size is a key parameter for drug-delivery nanoparticle design. It is believed that the size of a nanoparticle may have important effects on its ability to overcome the transport barriers in biological tissues. Nonetheless, such effects remain poorly understood. Using a multiscale model, this work investigates particle size effects on the tissue distribution and penetration efficacy of drug-delivery nanoparticles.

Results

We have developed a multiscale spatiotemporal model of nanoparticle transport in biological tissues. The model implements a time-adaptive Brownian Dynamics algorithm that links microscale particle-cell interactions and adhesion dynamics to tissue-scale particle dispersion and penetration. The model accounts for the advection, diffusion, and cellular uptakes of particles. Using the model, we have analyzed how particle size affects the intra-tissue dispersion and penetration of drug delivery nanoparticles. We focused on two published experimental works that investigated particle size effects in in vitro and in vivo tissue conditions. By analyzing experimental data reported in these two studies, we show that particle size effects may appear pronounced in an in vitro cell-free tissue system, such as collagen matrix. In an in vivo tissue system, the effects of particle size could be relatively modest. We provide a detailed analysis on how particle-cell interactions may determine distribution and penetration of nanoparticles in a biological tissue.

Conclusion

Our work suggests that the size of a nanoparticle may play a less significant role in its ability to overcome the intra-tissue transport barriers. We show that experiments involving cell-free tissue systems may yield misleading observations of particle size effects due to the absence of advective transport and particle-cell interactions.

     

Uptake and cellular distribution,in four plant species,of fluorescently labeled mesoporous silica nanoparticles

Key message

We report the uptake of MSNs into the roots and their movement to the aerial parts of four plant species and their quantification using fluorescence, TEM and proton-induced x - ray emission (micro - PIXE) elemental analysis.

Abstract

Monodispersed mesoporous silica nanoparticles (MSNs) of optimal size and configuration were synthesized for uptake by plant organs, tissues and cells. These monodispersed nanoparticles have a size of 20 nm with interconnected pores with an approximate diameter of 2.58 nm. There were no negative effects of MSNs on seed germination or when transported to different organs of the four plant species tested in this study. Most importantly, for the first time, a combination of confocal laser scanning microscopy, transmission electron microscopy and proton-induced X-ray emission (micro-PIXE) elemental analysis allowed the location and quantification MSNs in tissues and in cellular and sub-cellular locations. Our results show that MSNs penetrated into the roots via symplastic and apoplastic pathways and then via the conducting tissues of the xylem to the aerial parts of the plants including the stems and leaves. The translocation and widescale distribution of MSNs in plants will enable them to be used as a new delivery means for the transport of different sized biomolecules into plants.     

Different capacity of monocyte subsets to phagocytose iron-oxide nanoparticles

Objective

To explore the capacity of human CD14⁺CD16⁺⁺ and CD14⁺⁺CD16^- monocytes to phagocyte iron-oxide nanoparticles in vitro.

Methods

Human monocytes were labeled with four different magnetic nanoparticle preparations (Ferumoxides, SHU 555C, CLIO-680, MION-48) exhibiting distinct properties and cellular uptake was quantitatively assessed by flow cytometry, fluorescence microscopy, atomic absorption spectrometry and Magnetic Resonance Imaging (MRI). Additionally we determined whether cellular uptake of the nanoparticles resulted in phenotypic changes of cell surface markers.

Results

Cellular uptake differed between the four nanoparticle preparations. However for each nanoparticle tested, CD14⁺⁺CD16^- monocytes displayed a significantly higher uptake compared to CD14⁺CD16⁺⁺ monocytes, this resulted in significantly lower T1 and T2 relaxation times of these cells. The uptake of iron-oxide nanoparticles further resulted in a remarkable shift of expression of cell surface proteins indicating that the labeling procedure affects the phenotype of CD14⁺CD16⁺⁺ and CD14⁺⁺CD16^- monocytes differently.

Conclusion

Human monocyte subsets internalize different magnetic nanoparticle preparations differently, resulting in variable loading capacities, imaging phenotypes and likely biological properties.     

Electric field effect on the zigzag (6,0) single-wall BC2N nanotube for use in nano-electronic circuits

We have analyzed the effect of external electric field on the zigzag (6,0) single-wall BC₂N nanotube using density functional theory calculations. Analysis of the structural parameters indicates that the nanotube is resistant against the external electric field strengths. Analysis of the electronic structure of the nanotube indicates that the applied parallel electric field strengths have a much stronger interaction with the nanotube with respect to the transverse electric field strengths and the nanotube is easier to modulate by the applied parallel electric field. Our results show that the properties of the nanotube can be controlled by the proper external electric field for use in nano-electronic circuits.

Nanoparticle biofabrication using English ivy (Hedera helix)

Background

English ivy (Hedera helix) is well known for its adhesive properties and climbing ability. Essential to its ability to adhere to vertical surfaces is the secretion of a nanocomposite adhesive containing spherical nanoparticles, 60?C85 nm in diameter, produced exclusively by root hairs present on adventitious roots. These organic nanoparticles have shown promise in biomedical and cosmetic applications, and represent a safer alternative to metal oxide nanoparticles currently available.

Results

It was discovered that the maximum adventitious root production was achieved by a 4 h application of 1 mg/ml indole-3 butyric acid (IBA) to juvenile English ivy shoot segments cultured in custom vessels. After incubation of the shoots under continuous light at 83 ??mol/m² s at 20°C for 2 weeks, the adventitious roots were harvested from the culture system and it was possible to isolate 90 mg of dry weight nanoparticles per 12 g of roots. The nanoparticle morphology was characterized by atomic force microscopy, and found to be similar to previous studies.

Conclusions

An enhanced system for the production of English ivy adventitious roots and their nanoparticles by modifying GA7 Magenta boxes and identifying the optimal concentration of IBA for adventitious root growth was developed. This system is the first such platform for growing and harvesting organic nanoparticles from plants, and represents an important step in the development of plant-based nanomanufacturing. It is a significant improvement on the exploitation of plant systems for the formation of metallic nanoparticles, and represents a pathway for the generation of bulk ivy nanoparticles for translation into biomedical applications.     

Magnetic core-shell nanoparticles for drug delivery by nebulization

Background

Aerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe₃O₄ magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.

Results

Average particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 μg/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.

Conclusion

We have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has implications for targeted delivery of therapeutics and poorly soluble medicinal compounds via inhalation route.     

The genome sequence of E. coli W (ATCC 9637): comparative genome analysis and an improved genome-scale reconstruction of E. coli

Background

The large number of genetic linkage maps representing Brassica chromosomes constitute a potential platform for studying crop traits and genome evolution within Brassicaceae. However, the alignment of existing maps remains a major challenge. The integration of these genetic maps will enhance genetic resolution, and provide a means to navigate between sequence-tagged loci, and with contiguous genome sequences as these become available.

Results

We report the first genome-wide integration of Brassica maps based on an automated pipeline which involved collation of genome-wide genotype data for sequence-tagged markers scored on three extensively used amphidiploid Brassica napus (2n = 38) populations. Representative markers were selected from consolidated maps for each population, and skeleton bin maps were generated. The skeleton maps for the three populations were then combined to generate an integrated map for each LG, comparing two different approaches, one encapsulated in JoinMap and the other in MergeMap. The BnaWAIT_01_2010a integrated genetic map was generated using JoinMap, and includes 5,162 genetic markers mapped onto 2,196 loci, with a total genetic length of 1,792 cM. The map density of one locus every 0.82 cM, corresponding to 515 Kbp, increases by at least three-fold the locus and marker density within the original maps. Within the B. napus integrated map we identified 103 conserved collinearity blocks relative to Arabidopsis, including five previously unreported blocks. The BnaWAIT_01_2010a map was used to investigate the integrity and conservation of order proposed for genome sequence scaffolds generated from the constituent A genome of Brassica rapa.

Conclusions

Our results provide a comprehensive genetic integration of the B. napus genome from a range of sources, which we anticipate will provide valuable information for rapeseed and Canola research.     

Effect of heat dissipation of superparamagnetic nanoparticles in alternating magnetic field on three human cancer cell lines in magnetic fluid hyperthermia

ABSTRACT

Purpose: The purpose of this study was to propose a method for constructing the software setup required for investigating thermal effect of superparamagnetic nanoparticles on three human cell lines. This article aimed to examine the required nanoparticle dose, frequency, field intensity and the exposure time. Materials and methods: In the present study, first some general details were given about design and construction of the setup required for generating a safe magnetic field in order to examine the thermal effect of superparamagnetic nanoparticles on three human cancer cell lines, cultured under laboratory conditions. Next, a series of experimental tests were conducted to study the effect of magnetic field, on the cells. Finally, by applying three types of iron-based nanoparticles with mean diameters of 8, 15 and 20 nm, for 30 min, the temperature rise and specific absorption rate (SAR) were calculated. Results: By conducting experimental tests, the maximum temperature rise at the resonance frequency of the coil was reported to be 80 kHz, and it was observed that all the cells died when temperature of the cells reached 42°C/30 min. Based on the experiments, it was observed that magnetic field with intensity of 8 kA/m within the frequency range of 80–180 kHz did not have any effect on the cells. Conclusions: Based on the results, it can be concluded that the nanoparticle dose of 80 µg/ml with diameter of 8 nm at the resonance frequency of coil for 30 min was sufficient to destroy all the cancerous cells in the flask.     

Cubic Magnetically Guided Nanoaggregates for Inhalable Drug Delivery: In Vitro Magnetic Aerosol Deposition Study

The present work describes the in vitro aerosol deposition and enhanced deaggregation behavior of superparamagnetic iron oxide nanoaggregates (SPIONs). SPIONs were surface-coated with amine functionalized polyrotaxane and were proposed as a carrier for inhalation dry powders. Polyrotaxane is primarily composed of beta cyclodextrin rings which are spontaneously threaded on the block copolymer, poly(propylene glycol) bis(2-aminopropylether). Variable concentrations of surface coating polymers showed controlled manipulation of the crystal size and morphology. Magnetic nanoaggregates fabricated with low concentration of polyrotaxane showed cubic crystal morphology. However, these nanoaggregates exhibited rhombic dodecahedron crystal structure upon increasing the coating polymer concentration. In comparison to the spherical uncoated magnetic nanoparticles, cubic phase magnetic nanoaggregates demonstrated an enhanced in vitro aerosol deposition using magnetic field alignment. This enhancement can be accomplished at low inhalation flow rates (15 and 30 L/min). However, transformation to the cubic crystal structure was observed to be associated with a reduction in the powder geometric standard deviation. Using a mathematical modeling approach, we noted significant enhancement in the deaggregation behavior of inhalation dry powders; that can be achieved with small amounts of magnetic nanoaggregates. Aggregates of cubic nanoparticles showed promise for targeted pulmonary deposition of anticancer drugs.

A reference database for tumor-related genes co-expressed with interleukin-8 using genome-scale in silico analysis

Background

The EST database provides a rich resource for gene discovery and in silico expression analysis. We report a novel computational approach to identify co-expressed genes using EST database, and its application to IL-8.

Results

IL-8 is represented in 53 dbEST cDNA libraries. We calculated the frequency of occurrence of all the genes represented in these cDNA libraries, and ranked the candidates based on a Z-score. Additional analysis suggests that most IL-8 related genes are differentially expressed between non-tumor and tumor tissues. To focus on IL-8's function in tumor tissues, we further analyzed and ranked the genes in 16 IL-8 related tumor libraries.

Conclusions

This method generated a reference database for genes co-expressed with IL-8 and could facilitate further characterization of functional association among genes.