Amelioration of collagen-induced arthritis in rats by nanogold. (17/1513)

OBJECTIVE: Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen-induced arthritis (CIA) in rats. METHODS: Binding of 13-nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF-induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) in the ankle joints were determined. RESULTS: Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF-induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold-treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFalpha and IL-1beta were also significantly reduced in the ankle joints of nanogold-treated rats. CONCLUSION: Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.  (+info)

Intracellular distribution of TiO2-DNA oligonucleotide nanoconjugates directed to nucleolus and mitochondria indicates sequence specificity. (18/1513)

Deoxyribonucleic acid (DNA) oligonucleotides hybridize to matching DNA sequences in cells, as established in the literature, depending on active transcription of the target sequence and local molarity of the oligonucleotide. We investigated the intracellular distribution of nanoconjugates composed of DNA oligonucleotides attached to TiO2 nanoparticles, thus creating a locally increased concentration of the oligonucleotide. Two types of nanoconjugates, with oligonucleotides matching mitochondrial or nucleolar DNA, were specifically retained in mitochondria or nucleoli.  (+info)

Label-free direct electronic detection of biomolecules with amorphous silicon nanostructures. (19/1513)

We present the fabrication and characterization of a nano-scale sensor made of amorphous silicon for the label-free, electronic detection of three classes of biologically important molecules: ions, oligonucleotides, and proteins. The sensor structure has an active element which is a 50 nm wide amorphous silicon semicircle and has a total footprint of less than 4 microm2. We demonstrate the functionalization of the sensor with receptor molecules and the electronic detection of three targets: H(+) ions, short single-stranded DNAs, and streptavidin. The sensor is able to reliably distinguish single base-pair mismatches in 12 base long strands of DNA and monitor the introduction and identification of straptavidin in real-time. The versatile sensor structure can be readily functionalized with a wide range of receptor molecules and is suitable for integration with high-speed electronic circuits as a post-process on an integrated circuit chip.  (+info)

Synthesis, characterization, and bioavailability in rats of ferric phosphate nanoparticles. (20/1513)

Particle size is a determinant of iron (Fe) absorption from poorly soluble Fe compounds. Decreasing the particle size of metallic Fe and ferric pyrophosphate added to foods increases Fe absorption. The aim of this study was to develop and characterize nanoparticles of FePO(4) and determine their bioavailability and potential toxicity in rats. Amorphous FePO(4) nanopowders with spherical structure were synthesized by flame spray pyrolysis (FSP). The nanopowders were characterized and compared with commercially available FePO(4) and FeSO(4), including measurements of specific surface area (SSA), structure by transmission electron microscopy, in vitro solubility at pH 1 and 2, and relative bioavailability value (RBV) to FeSO(4) in rats using the hemoglobin repletion method. In the latter, the potential toxicity after Fe repletion was assessed by histological examination and measurement of thiobarbituric acid reactive substances (TBARS). The commercial FePO(4) and the 2 FePO(4) produced by FSP (mean particle sizes, 30.5 and 10.7 nm) had the following characteristics: SSA: 32.6, 68.6, 194.7 m(2)/g; in vitro solubility after 30 min at pH 1: 73, 79, and 85% of FeSO(4); and RBV: 61, 70, and 96%, respectively. In the histological examinations and TBARS analysis, there were no indications of toxicity. In conclusion, nanoparticles of FePO(4) have a solubility and RBV not significantly different from FeSO(4). Reducing poorly soluble Fe compounds to nanoscale may increase their value for human nutrition.  (+info)

Single cell fluorescence imaging using metal plasmon-coupled probe. (21/1513)

This work constitutes the first fluorescent imaging of cells using metal plasmon-coupled probes (PCPs) at single cell resolution. N-(2-Mercapto-propionyl)glycine-coated silver nanoparticles were synthesized by reduction of silver nitrate using sodium borohyride and then succinimidylated via ligand exchange. Alexa Fluor 647-labeled concanavalin A (con A) was chemically bound to the silver particles to make the fluorescent metal plasmon-coupled probes. The fluorescence images were collected using a scanning confocal microscopy. The fluorescence intensity was observed to enhance 7-fold when binding the labeled con A on a single silver particle. PCPs were conjugated on HEK 293 A cells. Imaging results demonstrate that cells labeled by PCPs were 20-fold brighter than those by free labeled con A.  (+info)

Penetration of metallic nanoparticles in human full-thickness skin. (22/1513)

The potential and benefits of nanoparticles in nanobiotechnology have been enthusiastically discussed in recent literature; however, little is known about the potential risks of contamination by accidental contact during production or use. Although theories of transdermal drug delivery suggest that skin structure and composition do not allow the penetration of materials larger than 600 Da, some articles on particle penetration into the skin have been recently published. Consequently, we wanted to evaluate whether metallic nanoparticles smaller than 10 nm could penetrate and eventually permeate the skin. Two different stabilized nanoparticle dispersions were applied to excised human skin samples using vertical diffusion cells. At established time points, solutions in receiving chambers were quantified for nanoparticle concentration, and skin was processed for light transmission and electron microscope examination. The results of this study showed that nanoparticles were able to penetrate the hair follicle and stratum corneum (SC), occasionally reaching the viable epidermis. Yet, nanoparticles were unable to permeate the skin. These results represent a breakthrough in skin penetration because it is early evidence where rigid nanoparticles have been shown to passively reach the viable epidermis through the SC lipidic matrix.  (+info)

Ultrasensitive densitometry detection of cytokines with nanoparticle-modified aptamers. (23/1513)

BACKGROUND: Aptamers mimic properties of antibodies and sometimes turn out to be even better than antibodies as reagents for assays. We describe the establishment of an ultrasensitive densitometry method for cytokine detection by nanoparticle (NP)-modified aptamers. METHODS: The assay simultaneously uses a gold NP-modified aptamer and a biotin-modified aptamer to bind to the target protein, forming a sandwich complex. The absorbance signal generated by the aptamer-protein complex is amplified and detected with a microplate reader. RESULTS: The assay for platelet-derived growth factor B-chain homodimer (PDGF-BB) was linear from 1 fmol/L to 100 pmol/L (R(2) = 0.9869). The analytical detection limit was 83 amol/L. The intraassay and interassay imprecision (CVs) was < or =7.5%. Serum concentrations of PDGF-BB determined with the gold NP-modified aptamer assay and with ELISA were not significantly different. CONCLUSIONS: The gold NP-modified aptamer assay provides a fast, convenient method for cytokine detection and improves the detection range and the detection limit compared with ELISA.  (+info)

The present status of cell tracking methods in animal models using magnetic resonance imaging technology. (24/1513)

With the advance of stem cell transplantation research, in vivo cell tracking techniques have become increasingly important in recent years. Magnetic resonance imaging (MRI) may provide a unique tool for non-invasive tracking of transplanted cells. Since the initial findings on the stem cell migration by MRI several years ago, there have been numerous studies using various animal models, notably in heart or brain disease models. In order to develop more reliable and clinically applicable methodologies, multiple aspects should be taken into consideration. In this review, we will summarize the current status and future perspectives of in vivo cell tracking technologies using MRI. In particular, use of different MR contrast agents and their detection methods using MRI will be described in much detail. In addition, various cell labeling methods to increase the sensitivity of signals will be extensively discussed. We will also review several key experiments, in which MRI techniques were utilized to detect the presence and/or migration of transplanted stem cells in various animal models. Finally, we will discuss the current problems and future directions of cell tracking methods using MRI.  (+info)