Albena Ivanisevic

A mesoporous silica nanosphere-based drug delivery system using an electrically conducting polymer.

In this study, a mesoporous silica nanoparticle (MSN)-based nerve growth factor (NGF) delivery system has been successfully embedded within an electroactive polypyrrol (Ppy). The spherical particles with approximately 100 nm diameter possess a large surface-to-volume ratio for the entrapment of NGF into the pores of MSNs while retaining their bioactivity. Direct incorporation of MSN-NGF within Ppy was achieved during electrochemical polymerization. The loading amount and release profile of NGF from the composite was investigated by sandwich ELISA. The NGF incorporation can be controllable by varying particle concentration or by extending electrodeposition time. The morphology and chemical composition of the Ppy/MSN-NGF composite was evaluated by atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and x-ray photoelectron spectroscopy (XPS). Optical and electron microscopy revealed a characteristic attachment of PC 12 cells and the outgrowth of their neurites when grown on the Ppy/MSN-NGF composite as a result of a sustained and controlled release of NGF. In order to observe the effectiveness of electrical stimulation, neurite extension of cells cultured on unstimulated and stimulated Ppy/MSN-NGF was compared. The NGF release in the presence of electrical stimulation promoted significantly greater neurite extension.

Repairing the damaged spinal cord and brain with nanomedicine.

There is no medical therapy for severe spinal-cord or brain injury that can restore behavioral loss in the chronic condition, or rapidly repair the membranes of damaged nerve cells in the acute stage of the injury. The latter permits rapid recovery of physiological functioning after injury, and largely vitiates continuing and progressive cell death. Here we describe for the first time a microcolloid composite, ranging from 50 to 300 nm, made of nonbiological, inert, and nontoxic components that fulfill all of the requirements of the latter therapy. From an applied-engineering standpoint, tools fabricated by nanotechnology have the potential to lead to more effective ways to treat and predict disease, though a particular therapy for central nervous system (CNS) injury or disease has yet to be realized. Recent activity in nanotechnology has substantially improved colloid-based systems. The versatility of materials with inherent unique properties (optical, electrical, magnetic, and chemical) can be realized with the incorporation of a variety of biocompatible and biodegradable materials such as synthetic or natural polymers, lipids, or solid (metal, semiconductor, magnetic, or insulator) components. Of these, silica particles have several advantages: i) they ride upon a wealth of well-established methods for the synthesis and incorporation with other substances through surface modification and bioconjugation; ii) they have great potential to perform multifunctional activity; and iii) they exhibit intrinsic hydrophilicity, biocompatibility, and nontoxicity. In addition, inorganic cores, rather than organic cores such as micelles, have a longer ‘‘shelf life’’.

Functional silica nanoparticle‐mediated neuronal membrane sealing following traumatic spinal cord injury

The mechanical damage to neurons and their processes induced by spinal cord injury (SCI) causes a progressive cascade of pathophysiological events beginning with the derangement of ionic equilibrium and collapse of membrane permeability. This leads to a cumulative deterioration of neurons, axons, and the tissue architecture of the cord. We have previously shown that the application of the hydrophilic polymer polyethylene glycol (PEG) following spinal cord or brain injury can rapidly restore membrane integrity, reduce oxidative stress, restore impaired axonal conductivity, and mediate functional recovery in rats, guinea pigs, and dogs. However there are limits to both the concentration and the molecular weight of the application that do not permit the broadest recovery across an injured animal population. In this study, PEG‐decorated silica nanoparticles (PSiNPs) sealed cells, as shown by the significantly reduced leakage of lactate dehydrogenase from damaged cells compared with uncoated particles or PEG alone. Further in vivo tests showed that PSiNPs also significantly reduced the formation of reactive oxygen species and the process of lipid peroxidation of the membrane. Fabrication of PSiNPs containing embedded dyes also revealed targeting of the particles to damaged, but not undamaged, spinal cord tissues. In an in vivo crush/contusion model of guinea pig SCI, every animal but one injected with PSiNPs recovered conduction through the cord lesion, whereas none of the control animals did. These findings suggest that the use of multifunctional nanoparticles may offer a novel treatment approach for spinal cord injury, traumatic brain injury, and possibly neurodegenerative disorders.

Biosensing: Taking charge of biomolecules

The combination of two scanning probe microscopy techniques has led to a label-free method of detecting charged molecules at the nanoscale and offers a general approach to biosensing with improved resolution, sensitivity and speed.

Circular Dichroism Study of the Mechanism of Formation of DNA Templated Nanowires

In order to control the fabrication method, the mechanism used in the formation of DNA templated nanowires is investigated through circular dichroism (CD) spectroscopy. Metallic (Au) and magnetic (Fe(2)O(3) and CoFe(2)O(4)) nanoparticles (NP) are aligned along the DNA strand at various mass ratios. The DNA templated nanowires are compared to the structure of B-form dsDNA through CD experiments. Absorbance and thermal melting tests are performed to verify the structural changes of DNA templated nanowires. Low concentrations of nanoparticles preserve the DNA B-form through electrostatic interactions. Conversely, at higher concentrations of nanoparticles aligned along the DNA strand, the template is denatured. Information on the mode of nanoparticle binding and DNA helix alterations are explored for metallic and magnetic nanowires based upon the results.

Magnetic wires with DNA cores: A magnetic force microscopy study

Magnetic force microscopy (MFM) has been employed to study Fe3O4 nanowires containing DNA cores. The MFM experiments confirmed that long DNA molecules templated with Fe3O4 nanoparticles form a magnetic wire. The components of wires containing particles with sizes below 10 nm were recorded to behave as single domain particles with out-of-plane magnetization. The MFM study showed that one can change the magnetization states of the particles using a magnetic tip. The properties of the magnetic wires with DNA cores make them an attractive material for future magnetostatic devices.

Characterizing proton relaxation times for metallic and magnetic layer-by-layer-coated, DNA-templated nanoparticle chains

Metallic and superparamagnetic DNA-templated nanoparticle (NP) chains are examined as potential imaging agents. Proton relaxation times (T(1) and T(2)) are measured for DNA nanostructures using nuclear magnetic resonance (NMR) spectroscopy. The layer-by-layer (LBL) method was used to encapsulate the DNA-templated NP chains and demonstrated a change in proton relaxation times. Results from this study suggest that LBL-coated, DNA-templated nanostructures can serve as effective imaging agents for magnetic resonance imaging (MRI) applications.

Light-emitting diodes as chemical sensors.

The systematic testing of slaughtered cattle aged over 30 months, or alternatively their elimination from the food chain, is an important component of a package of measures introduced in the European Union on 1 January 2001 to combat bovine spongiform encephalopathy (BSE) and protect human health. Here we explore the analytical limit of a rapid test designed to detect the abnormal prion protein associated with BSE in bovine brain and find that it is comparable to the limit of detection of infectivity in the conventional mouse bioassay1, which is impractical for systematic screening. The sensitivity of the biochemical test allows it to be used as a viable alternative to the destruction of all carcasses of cattle slaughtered after 30 months of age. Additional work is required to compare this analytical sensitivity with the diagnostic sensitivity of the test under conditions of routine post-mortem BSE diagnosis and surveillance.es with active-layer thickness, reaching several hundred per cent for the double heterostructures with the thickest active layer. The reversible responses (Fig. 1b) demonstrate the potential for online sensing with these structures. All of the analyte– diode structure combinations displayed adsorption and desorption times of less than a few minutes at room temperature. For all analytes, enhancements are seen at pressures as low as about 0.01 torr, with the response saturating at around 0.1–1 torr. The electroluminescent response is reproducible even after weeks of storage in air. This adsorbate-induced modulation of electroluminescent intensity from simple double-heterostructure diodes illustrates their application as transducers that can couple semiconductor surface chemistry to an optical signal. The remarkable features of these structures (robust, inexpensive, small, low power consumption, compositionally tunable emission spectra) could allow arrays to be used to identify a variety of analytes. Highly sensitive, ultrasmall LEDs with large surface-to-volume ratios should then be easily integrated with diodes that serve as photodetectors, forming monolithic chemical sensors. From photoluminescent studies of semiconductors and from electroluminescence of molecular diodes, it should be possible to customize the selectivity, sensitivity and speed of the electroluminescent response by surface modification. Albena Ivanisevic*, Jeng-Ya Yeh†, Luke Mawst†, Thomas F. Kuech‡, Arthur B. Ellis* Departments of *Chemistry, †Electrical and Computer Engineering and ‡Chemical Engineering, University of Wisconsin, Madison, Wisconsin 53706, USA

Gold–iron oxide nanoparticle chains scaffolded on DNA as potential magnetic resonance imaging agents

We present a unique nanostructure design using DNA that can serve as potential magnetic resonance imaging (MRI) agents. By attaching gold and iron oxide NPs on linear strands of DNA, NP chains are easily formed by self-assembly and through DNA-based enzymes. Furthermore, gold–iron oxide NP chains exhibit fast proton relaxation times that improve MRI signals and do not induce in vitro toxicity. This report highlights the use of DNA to create NP chains as a cost-effective, promising technology for the detection of diseases through MRI.

Modification of native collagen with cell‐adhesive peptide to promote RPE cell attachment on Bruch's membrane

Current efforts to reverse loss of visual function due to Age-related Macular Degeneration point to the restoration of the Retinal Pigment Epithelial (RPE) layer. Restoration of the RPE layer involves replacing lost RPE cells as well as addressing the degeneration of the underlying Bruchs membrane (BM). To advance the potential of using donor BM, we present a strategy to achieve specific and controllable modification of the inner collagenous layer (ICL) of the Bruchs membrane. In particular, interaction between a collagen binding peptide (CBP) sequence with exposed collagen fibers on the ICL surface is utilized to anchor bioactive molecules. Here, a cell-adhesion sequence is added to the collagen binding sequence to promote attachment and survival of ARPE-19. First, the binding specificity of the CBP sequence is verified with a fluorescent binding assay. Subsequently, the effect of modification using the peptide is studied qualitatively using confocal fluorescent imaging and quantitatively through a cell proliferation assay. Results of these experiments indicate that the peptide sequence binds specifically to collagen fibers. Additionally, modification using the peptide enhanced cell adhesion, allowing large uniform cell networks to be formed on the surface. Furthermore, modification with the peptide also delayed the onset of apoptosis on adherent cells.