Biocompatibility, Pharmaceutical and Biomedical Applications L. Harivardhan Reddy,†,‡ Jose ́ L. Arias, Julien Nicolas,† and Patrick Couvreur*,† †Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Universite ́ Paris-Sud XI, UMR CNRS 8612, Faculte ́ de Pharmacie, IFR 141, 5 rue Jean-Baptiste Cleḿent, F-92296 Chat̂enay-Malabry, France Departamento de Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Campus Universitario de Cartuja s/n, Universidad de Granada, 18071 Granada, Spain ‡Pharmaceutical Sciences Department, Sanofi, 13 Quai Jules Guesdes, F-94403 Vitry-sur-Seine, France

Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications.

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Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy

Magnetic sensors can be classified according to whether they measure the total magnetic field or the vector components of the magnetic field. The techniques used to produce both types of magnetic sensors encompass many aspects of physics and electronics. Here, we describe and compare most of the common technologies used for magnetic field sensing. These include search coil, fluxgate, optically pumped, nuclear precession, SQUID, Hall-effect, anisotropic magnetoresistance, giant magnetoresistance, magnetic tunnel junctions, giant magnetoimpedance, magnetostrictive/piezoelectric composites, magnetodiode, magnetotransistor, fiber optic, magnetooptic, and microelectromechanical systems-based magnetic sensors. The usage of these sensors in relation to working with or around Earth's magnetic field is also presented

Magnetic sensors and their applications

Nanostructures have attracted huge interest as a rapidly growing class of materials for many applications. Several techniques have been used to characterize the size, crystal structure, elemental composition and a variety of other physical properties of nanoparticles. In several cases, there are physical properties that can be evaluated by more than one technique. Different strengths and limitations of each technique complicate the choice of the most suitable method, while often a combinatorial characterization approach is needed. In addition, given that the significance of nanoparticles in basic research and applications is constantly increasing, it is necessary that researchers from separate fields overcome the challenges in the reproducible and reliable characterization of nanomaterials, after their synthesis and further process (e.g. annealing) stages. The principal objective of this review is to summarize the present knowledge on the use, advances, advantages and weaknesses of a large number of experimental techniques that are available for the characterization of nanoparticles. Different characterization techniques are classified according to the concept/group of the technique used, the information they can provide, or the materials that they are destined for. We describe the main characteristics of the techniques and their operation principles and we give various examples of their use, presenting them in a comparative mode, when possible, in relation to the property studied in each case.

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Characterization techniques for nanoparticles: comparison and complementarity upon studying nanoparticle properties

A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to be resolved before they can be moved from bench top to bedside.

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Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

We developed a narrowband magnetic particle imaging (MPI) system that uses third-harmonic signal detection and electrical scanning of the field free point (FFP). Comparing with mechanical scanning, we can decrease the measurement time significantly and increase the signal-to-noise ratio as well. For electrical scanning, we designed and constructed gradient and shift coils. The gradient coil consisting of four pieces of planar coils generated the gradient field with a field gradient of 0.4 T/m at a height of 25 mm from the coil surface. The FFP can be moved ±8 mm by supplying a current of ±6.6 A to the shift coil. Using the developed system, we detected two magnetic nanoparticle (MNP) samples located at a depth of 35 mm below the pickup coil with a spacing of 10 mm. By applying an excitation field of 1 mT at 22.75 kHz, we measured the third-harmonic signal from the MNP samples and obtained a contour map of the signal field in an area of 16 $\times$ 16 mm2. Then, we converted the field map into an MNP distribution using singular value decomposition method. It was shown that the spatial resolution of the reconstructed MNP distribution was improved compared with that of the measured contour map of the signal field. The spatial resolution for MNP detection in MNP distribution was 5 mm and two MNP samples were distinguished clearly. This result indicated that MPI using electrical scanning of the FFP was successfully performed.

Narrowband Magnetic Particle Imaging Utilizing Electric Scanning of Field Free Point

Performances of high T/sub c/ dc SQUID utilizing bicrystal junctions with 30/spl deg/ misorientation angle have been studied. Junction resistance R/sub s/=10 /spl Omega/ and critical current I/sub 0/=10-20 /spl mu/A can be obtained rather easily at T=77 K with this technology. As a result, voltage modulation depth as high as 50 /spl mu/V, and flux noise as low as 5 /spl mu//spl Phi//sub 0//Hz/sup 1/2/ obtained for the 100 pH-SQUID. The measured values of the voltage modulation depth agree reasonably well with the numerical simulation, while the measured values of the flux noise are about 2 or 3 times larger than the simulation. The reason for the high noise level is discussed by taking into account imperfection of junctions.

High T/sub c/ dc SQUID utilizing bicrystal junctions with 30 degree misorientation angle

Thermally activated magnetic-flux entry into a pickup coil through a flux dam in high-Tc superconducting quantum interference device (SQUID) magnetometer is studied. Since the thermally activated flux entry strongly depends on the circulating current in the pickup coil, the behavior of the circulating current is studied with numerical simulation when an external field is applied. It is shown that the circulating current becomes near the critical current of the flux dam after the large external field is applied. In this case, thermally activated flux entry becomes large, and degrades the SQUID performance. In order to suppress the thermal activation, the circulating current must be much below the critical current. For this purpose, two methods are proposed. One is to use a compensation field in the case of the flux dam, and the other is to use a switch instead of the flux dam. Numerical simulation shows that we can rapidly decrease the circulating current much below the critical current, and hence, can sup...

Suppression of thermally activated flux entry through a flux dam in high Tc superconducting quantum interference device magnetometer

We measured spatial distributions of the trapped magnetic flux density B in polycrystalline YBaCuO superconductors. It is shown that the spatial distribution of B for external magnetic fields is similar to that predicted from the critical state model of the type II superconductor. Furthermore, the spatial gradient of B becomes steep in proportion to the coupling strength among superconducting grains. It is also shown that the spatial distribution of B changes when the grain-coupling strength is degraded by postannealing around 200°C.

Spatial Distribution of Trapped Magnetic Flux in the High- T c Superconductor Y 1 Ba 2 Cu 3 O 7−δ . II. Comparison with the Critical State Model

A comprehensive quantitative comparison between the measured performance of direct-coupled high Tc superconducting quantum interference device (SQUID) magnetometers with 30° bicrystal junctions and a numerical simulation is presented. It is shown that the characteristics of the SQUID magnetometer are considerably affected by resonances due to the large dielectric constant of the SrTiO3 substrate. In the realized magnetometer layout, the strip line resonance occurring in the SQUID inductance increases the voltage modulation depth and the output voltage noise of the SQUID, while the flux noise of the SQUID is nearly unchanged. It is also shown that the distortion of the voltage versus flux characteristic is caused by the LC resonance in the pickup loop of the magnetometer in combination with a capacitive feedback. Good agreement between experiment and simulation has been obtained.

Direct-Coupled High Tc DC Superconducting Quantum Interference Device Magnetometers on SrTiO3 Substrate: Theoretical Description and Comparison with Experiment

Keiji Enpuku

Papers

Narrowband Magnetic Particle Imaging Utilizing Electric Scanning of Field Free Point

High T/sub c/ dc SQUID utilizing bicrystal junctions with 30 degree misorientation angle

Suppression of thermally activated flux entry through a flux dam in high Tc superconducting quantum interference device magnetometer

Spatial Distribution of Trapped Magnetic Flux in the High- T c Superconductor Y 1 Ba 2 Cu 3 O 7−δ . II. Comparison with the Critical State Model

Direct-Coupled High Tc DC Superconducting Quantum Interference Device Magnetometers on SrTiO3 Substrate: Theoretical Description and Comparison with Experiment