Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications

This review focuses on the synthesis, protection, functionalization, and application of magnetic nanoparticles, as well as the magnetic properties of nanostructured systems. Substantial progress in the size and shape control of magnetic nanoparticles has been made by developing methods such as co-precipitation, thermal decomposition and/or reduction, micelle synthesis, and hydrothermal synthesis. A major challenge still is protection against corrosion, and therefore suitable protection strategies will be emphasized, for example, surfactant/polymer coating, silica coating and carbon coating of magnetic nanoparticles or embedding them in a matrix/support. Properly protected magnetic nanoparticles can be used as building blocks for the fabrication of various functional systems, and their application in catalysis and biotechnology will be briefly reviewed. Finally, some future trends and perspectives in these research areas will be outlined.

Magnetic nanoparticles: Synthesis, protection, functionalization, and application

1. Introduction 20642. Synthesis of Magnetic Nanoparticles 20662.1. Classical Synthesis by Coprecipitation 20662.2. Reactions in Constrained Environments 20682.3. Hydrothermal and High-TemperatureReactions20692.4. Sol-Gel Reactions 20702.5. Polyol Methods 20712.6. Flow Injection Syntheses 20712.7. Electrochemical Methods 20712.8. Aerosol/Vapor Methods 20712.9. Sonolysis 20723. Stabilization of Magnetic Particles 20723.1. Monomeric Stabilizers 20723.1.1. Carboxylates 20733.1.2. Phosphates 20733.2. Inorganic Materials 20733.2.1. Silica 20733.2.2. Gold 20743.3. Polymer Stabilizers 20743.3.1. Dextran 20743.3.2. Polyethylene Glycol (PEG) 20753.3.3. Polyvinyl Alcohol (PVA) 20753.3.4. Alginate 20753.3.5. Chitosan 20753.3.6. Other Polymers 20753.4. Other Strategies for Stabilization 20764. Methods of Vectorization of the Particles 20765. Structural and Physicochemical Characterization 20785.1. Size, Polydispersity, Shape, and SurfaceCharacterization20795.2. Structure of Ferro- or FerrimagneticNanoparticles20805.2.1. Ferro- and Ferrimagnetic Nanoparticles 20805.3. Use of Nanoparticles as Contrast Agents forMRI20825.3.1. High Anisotropy Model 20845.3.2. Small Crystal and Low Anisotropy EnergyLimit20855.3.3. Practical Interests of Magnetic NuclearRelaxation for the Characterization ofSuperparamagnetic Colloid20855.3.4. Relaxation of Agglomerated Systems 20856. Applications 20866.1. MRI: Cellular Labeling, Molecular Imaging(Inﬂammation, Apoptose, etc.)20866.2.

Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.

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Drug delivery and nanoparticles:applications and hazards

Core/Shell Nanoparticles: Classes, Properties, Synthesis Mechanisms, Characterization, and Applications

Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging (MRI) contrast agents or in drug delivery applications. In this study, a novel approach to prepare magnetic polymeric nanoparticles with magnetic core and polymeric shell using inverse microemulsion polymerization process is reported. Poly(ethyleneglycol) (PEG)-modified superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared inside the aqueous cores of AOT/n-Hexane reverse micelles and characterized by various physicochemical means such as transmission electron microscopy (TEM), infrared spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM), and ultraviolet/visible spectroscopy. The inverse microemulsion polymerization of a polymerizable derivative of PEG and a cross-linking agent resulted in a stable hydrophilic polymeric shell of the nanoparticles. The results taken together from TEM and AFM studies showed that the particles are spherical in shape with core-shell structure. The average size of the PEG-modified nanoparticles was found to be around 40-50 nm with narrow size distribution. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles with saturation magnetization values between 45-50 electromagnetic units per gram. The cytotoxicity profile of the nanoparticles on human dermal fibroblasts as measured by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the particles are nontoxic and may be useful for various in vivo and in vitro biomedical applications.

Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies

Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles.

The concept of drug delivery using magnetic nanoparticles greatly benefit from the fact that nanotechnology has developed to a stage that it makes possible not only to produce magnetic nanoparticles in a very narrow size distribution range with superparamagnetic properties but also to engineer particle surfaces to provide site specific delivery of drugs. The size and surface characteristics of the nanoparticles are crucial factors that determine the success of the particles when used in vivo. The aim of this study was to modify the surfaces of the magnetic nanoparticles with PEG to improve the biocompatibility of the nanoparticles by resisting protein adsorption and increasing their intracellular uptake. In this study, the poly(ethyleneglycol) (PEG) modified superparamagnetic iron oxide nanoparticles have been prepared and their influence on human dermal fibroblasts is assessed in terms of cell adhesion/viability, morphology, particle uptake and cytoskeletal organisation studies. Various techniques have been used to determine nanoparticle-cell interactions including light, fluorescence, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The modification of nanoparticle surface induced alterations in cell behaviour distinct from the unmodified particles, suggesting that cell response can be directed via specifically engineered particle surfaces.

Ajay Kumar Gupta

Papers

Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications

Recent advances on surface engineering of magnetic iron oxide nanoparticles and their biomedical applications

Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies

Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles.

Surface modified superparamagnetic nanoparticles for drug delivery: interaction studies with human fibroblasts in culture.