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 sensing techniques have been recently developed to detect biomarkers using magnetic nanoparticles (MNPs) in liquid-phase assays. In the case of alternating current (ac) magnetic susceptibility when detecting a low number of MNPs, the diamagnetic signal of water becomes a major problem at a low signal-to-noise ratio. Therefore, we developed a high-temperature superconducting-quantum-interference-device-based ac susceptibility measurement system that can detect third-harmonic signals from MNPs. On the basis of the nonlinear characteristic of MNPs with large ac magnetic excitation (1.06 kHz), the third-harmonic signal detection (3.18 kHz) of MNPs leads to the elimination of the diamagnetic signal of water. The system consists of excitation and gradiometer pickup coils and a multifunctional circuit device. To improve the signal-to-noise ratio of the third-harmonic measurement, the system has two cancelation functions regarding the fundamental magnetic field. The MNPs are magnetized by using the fundamental magnetic field using the excitation coil. Third-harmonic signals from the MNPs were then detected during the up-and-down movement of the MNPs. We evaluated the detection sensitivity of our system using MNPs. We confirmed that the limit of detection consistency of MNPs was 10 ng by using the third-harmonic measurement method.

Highly sensitive third-harmonic detection method of magnetic nanoparticles using an AC susceptibility measurement system for liquid-phase assay

The magnetite nanoparticles were synthesized through a process including dissolution of Fe(OH)2 and precipitation of an oxidized phase under ultrasonic irradiation in an aqueous solution. It was found that the ultrasonic irradiation accelerated the formation of magnetite. The crystallinity and magnetic properties of the magnetite particles synthesized under ultrasonic irradiation were better than those synthesized under mechanical stirring. The effects of dissolved gas and pH value were also studied. The dissolved gas was important to the effect of ultrasound on the formation of magnetite and the properties of particles were different when different gases were used as dissolved gas in the sonochemical synthesis of magnetite. The magnetite particles were successfully synthesized even at a neutral solution under ultrasonic irradiation. The low pH value delayed the formation of magnetite and affected the morphology of magnetite particles.

Sonochemical Synthesis of the Magnetite Nanoparticles in Aqueous Solution

We have evaluated the use of harmonic signals for detecting magnetic nanoparticles (MNPs) in biomedical applications. We studied the relationship between the harmonic signals and the distribution of magnetic moments in MNP samples. We measured the harmonic signals and frequency dependence of the ac susceptibility along with static M-H curves. These experimental results were analyzed to obtain the magnetic moment distribution in real samples. We were able to clarify what proportion of MNPs contributes to the harmonic signal. MNPs could be classified according to three types. Type-1 contributes to the fundamental signal only. Type-2 contributes to both the fundamental and harmonic signals. Finally, Type-3 does not contribute to any signals. It is important to choose a sample having a large portion of Type-2 MNPs for the harmonic signal-based detection.

Evaluation of Harmonic Signals for the Detection of Magnetic Nanoparticles

We have proposed a method to evaluate the magnetic penetration depth and the surface resistance of superconducting thin films from the kinetic inductance measurement using coplanar waveguides. The method utilizes the coplanar waveguide resonator where the temperature dependence of the resonant frequency due to the kinetic inductance is measured. Comparison between the observed data and an analytical expression using a conformal mapping technique gives the value of the magnetic penetration depth. The magnetic penetration depth of NbN thin films obtained in this way is shown to be in excellent agreement with that estimated from the dirty limit theory using resistivity and critical temperature. By applying this method to a YBaCuO resonator, we obtained the magnetic penetration depth /spl lambda/(0)=266 nm for a c-axis oriented film. Using the two-fluid model it is also shown that the surface resistance of the film can be evaluated from the quality factor and the kinetic inductance. We obtained the residual surface resistance Rs(0)=20 /spl mu//spl Omega/ at a frequency of 3.8 GHz. >

Evaluation of magnetic penetration depth and surface resistance of superconducting thin films using coplanar waveguides

We studied the distributions of the magnetic moment and magnetic volume of magnetic nanoparticles (MNPs). These distributions were estimated by applying the singular value decomposition method to the M-H curve measured in the liquid phase. The estimated distributions were compared with a mixture of log-normal distributions, and two results agree well with each other. Using the estimated distribution of the magnetic moment, we also analyzed the M-H curve of immobilized MNPs in order to estimate the average value of the anisotropy energy constant Ku and the characteristic time τON that determines the Neel relaxation of immobilized MNPs. The values Ku and τON are estimated as 4 kJ/m3 and 1×10−9 s, respectively, for Resovist MNPs.

Keiji Enpuku

Papers

Highly sensitive third-harmonic detection method of magnetic nanoparticles using an AC susceptibility measurement system for liquid-phase assay

Sonochemical Synthesis of the Magnetite Nanoparticles in Aqueous Solution

Evaluation of Harmonic Signals for the Detection of Magnetic Nanoparticles

Evaluation of magnetic penetration depth and surface resistance of superconducting thin films using coplanar waveguides

Comparison of volume distribution of magnetic nanoparticles obtained from M-H curve with a mixture of log-normal distributions