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

High-temperature solution phase reaction of iron(III) acetylacetonate, Fe(acac)3, with 1,2-hexadecanediol in the presence of oleic acid and oleylamine leads to monodisperse magnetite (Fe3O4) nanoparticles. Similarly, reaction of Fe(acac)3 and Co(acac)2 or Mn(acac)2 with the same diol results in monodisperse CoFe2O4 or MnFe2O4 nanoparticles. Particle diameter can be tuned from 3 to 20 nm by varying reaction conditions or by seed-mediated growth. The as-synthesized iron oxide nanoparticles have a cubic spinel structure as characterized by HRTEM, SAED, and XRD. Further, Fe3O4 can be oxidized to Fe2O3, as evidenced by XRD, NEXAFS spectroscopy, and SQUID magnetometry. The hydrophobic nanoparticles can be transformed into hydrophilic ones by adding bipolar surfactants, and aqueous nanoparticle dispersion is readily made. These iron oxide nanoparticles and their dispersions in various media have great potential in magnetic nanodevice and biomagnetic applications.

Monodisperse MFe2O4 (M = Fe, Co, Mn) Nanoparticles

The physical principles underlying some current biomedical applications of magnetic nanoparticles are reviewed. Starting from well-known basic concepts, and drawing on examples from biology and biomedicine, the relevant physics of magnetic materials and their responses to applied magnetic fields are surveyed. The way these properties are controlled and used is illustrated with reference to (i) magnetic separation of labelled cells and other biological entities; (ii) therapeutic drug, gene and radionuclide delivery; (iii) radio frequency methods for the catabolism of tumours via hyperthermia; and (iv) contrast enhancement agents for magnetic resonance imaging applications. Future prospects are also discussed.

https://iopscience.iop.org/article/10.1088/0022-3727/36/13/201/pdf

Applications of magnetic nanoparticles in biomedicine

Single‐Step Nanoengineering of Silica Coated Maghemite Hollow Spheres with Tunable Magnetic Properties

Uniform α–Fe2O3 particles of varying axial ratios have been prepared from hydrolyzed ferric chloride solutions at 100 °C. In the absence of phosphate anions, spherical particles were obtained by a mechanism that follows the classical LaMer and Dinegar scheme. However, in the presence of phosphates ellipsoidal particles were observed, with their formation taking place through an aggregation process from smaller primary particles of α–Fe2O3. It is also shown that all particles are monocrystalline irrespective of their formation mechanism.

The formation of a–Fe2O3 monodispersed particles in solution

Barium ferrite nanoparticles prepared directly by aerosol pyrolysis

Preparation of uniform γ-Fe2O3 particles with nanometer size by spray pyrolysis

Colloidal suspensions of iron oxide and metal iron nanoparticles prepared by laser pyrolysis have been obtained by coating the particles with dextran in an aqueous media giving rise to biocompatible ferrofluids. The structural characteristics of the powders and the size of the particles and the aggregates in the colloidal suspensions have been analysed and correlated with the magnetic properties of both solids and fluids. For the first time, to our knowledge, a stable ferrofluid based on metal particles (<10?nm) has been obtained with aggregate sizes of ?nm. In comparison to iron oxide based products, this material exhibits higher saturation magnetization (45?emu?g?1) and susceptibilities (4000?emu/g?T). In addition, the nuclear magnetic resonance response of the ferrofluids has been measured in order to gain information about the influence of the crystallochemical and magnetic properties on their relaxation behaviour. The main parameter affected by the presence of the magnetic nanoparticles is the transversal relaxation time T2 and the corresponding relaxivity R2 value that is of the order of 400?(mmol/l)?1?s?1. It has been shown that R2 value increases not only by using iron metal instead of iron oxide but also by increasing the crystal size of the particles. From this study an evaluation of the possibilities of these materials as contrast agents for magnetic resonance imaging has been made.

https://iopscience.iop.org/article/10.1088/0957-4484/15/4/008/pdf

T. González-Carreño

Papers

Single‐Step Nanoengineering of Silica Coated Maghemite Hollow Spheres with Tunable Magnetic Properties

The formation of a–Fe2O3 monodispersed particles in solution

Barium ferrite nanoparticles prepared directly by aerosol pyrolysis

Preparation of uniform γ-Fe2O3 particles with nanometer size by spray pyrolysis

Comparative study of ferrofluids based on dextran-coated iron oxide and metal nanoparticles for contrast agents in magnetic resonance imaging