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

Magnetic particle imaging (MPI) utilizing nonlinear magnetization of magnetic nanoparticles (MNPs) is a new technique for in vivo diagnosis in medical imaging. We have improved a narrow-band MPI system using an orthogonal gradient field and third-harmonic signal detection. An AC excitation field with Bac = 1 mT and f = 22.75 kHz was applied, and a third-harmonic signal from MNPs (f = 68.75 kHz) was detected. The sensitivity of detection was improved by choosing proper diameter of a pickup coil so that we could detect 100 g of MNPs located as deep as z = 50 mm. A spatial resolution of ~4 mm was achieved by using a gradient field of 1 T/m. We demonstrated the detection of two MNP samples spaced 5 mm apart and located at z = 50 mm. The measured contour map of the voltage signal was converted to an MNP distribution using the singular value decomposition (SVD) method. We were able to accurately identify two MNP samples. We also demonstrate the imaging of the letter \"K\" composed of eleven MNP samples with 7-mm spacing, which demonstrated the validity of the present method.

Narrow-Band Magnetic Nanoparticle Imaging using Orthogonal Gradient Field

An imaging method based on the second harmonic (Bs2) signal detection from the magnetic nanoparticles (MNPs) has been developed to be applied for the Sentinel Lymph Node (SLN) detection during the breast cancer diagnosis. SLN can be detected by measuring the magnetic field signal of the injected MNPs tracer inside the body, instead of the conventional methods such as radioisotopes and/or blue dye tracers. The position and amount of MNPs accumulated at the SLNs are determined based on the magnetic field map measurement. The developed system can detect until 100-μg MS1 type-MNP sample located at a depth of 30 mm from the detection coil. Future improvements on the system and MNPs selection could further increase the detection sensitivity. MNPs that are accumulated at the deeper position under the body’s surface can be detected and distinguished with higher spatial resolution.

Harmonic signal detection based magnetic nanoparticle imaging system for breast cancer diagnosis

In order to realize an efficient coupling between a flux-flow-type Josephson oscillator (FFO) and a stripline, we have carried out experiments to verify the mathematical model of the inductive coupling scheme between FFO and a stripline resonator in the frequency range between 50 GHz and 350 GHz. It is shown that the simulation using the proposed equivalent circuit for the inductive coupling scheme well explains the experimental results. The experimentally obtained center frequency and the bandwidth of the matching circuit were as large as 120 GHz and 40 GHz, respectively, which are also in reasonable agreement with those obtained in the simulation.

Verification of the model of inductive coupling between a josephson oscillator and a stripline

We have investigated the fabrication of a high-temperature superconducting (HTS) gradiometer with long baseline for geophysical applications. The proof-of-concept gradiometer using a 1-turn pickup coil made of a GdBa 2 Cu 3 O y coated conductor (GCC) and 5.5-turn input coil integrated on a SQUID was fabricated in our previous work. In this study, we have optimized the device structure to improve the frequency response, gradient field sensitivity and gradiometer balance. The fabricated flux transformer consists of a 6-turn planar gradiometric pickup coil and a 26-turn input coil made of an HTS thin film. A low-melting-point alloy was used to connect polished Ag surfaces of the CGG pickup coil and Au pads of the input coil. An HTS SQUID was formed on another substrate and stacked on the input coil. A mechanical balancing structure using three pieces of GCC as a superconducting shield was also implemented. The fabricated gradiometer showed a gradient field noise of 0.8 fT/cm Hz 1/2 in the white noise regions, a gradiometer balance of 1/142, and a cutoff frequency of 9 Hz corresponding to a 2 mΩ contact resistance between the pickup coil and the input coil.

HTS planar gradiometer consisting of SQUID with multi-turn input coil and large pickup coil made of GdBCO coated conductor

Magnetic-flux trapping in Pb-alloy thin films is studied experimentally. In order to clarify pinning characteristics of thin films, which dominate flux trapping, trapped flux in Pb-alloy thin films is measured in-situ from the increment of the quasiparticle current of the Josephson junction made of these Pb-alloy thin films. Experimental results are discussed with the critical state model based on the pinning theory of superconductors. From the material dependence of flux trapping, it is shown that the addition of Au to Pb increases flux trapping due to the occurence of strong pinning centers of normal precipitates of AuPb2 and AuPb3 etc. It is also shown that the addition of Bi decreases flux trapping due to the large value of the London penetration depth of PbBi films. From the temperature dependence of flux trapping, it is shown that the amount of the trapped flux is reduced by raising the temperature of thin films. Finally, the effect of the trapped flux in junction electrodes on the suppression of the critical current of the junction is discussed quantitatively.

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Keiji Enpuku

Papers

Narrow-Band Magnetic Nanoparticle Imaging using Orthogonal Gradient Field

Harmonic signal detection based magnetic nanoparticle imaging system for breast cancer diagnosis

Verification of the model of inductive coupling between a josephson oscillator and a stripline

HTS planar gradiometer consisting of SQUID with multi-turn input coil and large pickup coil made of GdBCO coated conductor

Flux-Trapping Characteristics of Pb-alloy Superconducting Thin Films for Josephson Tunnel Junctions