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

TOPICAL REVIEW: Applications of magnetic nanoparticles in biomedicine

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

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.

Magnetic nanoparticles have attracted attention because of their current and potential usefulness as contrast agents for magnetic resonance imaging (MRI) or colloidal mediators for cancer magnetic hyperthermia. This review examines these in vivo applications through an understanding of the involved problems and the current and future possibilities for resolving them. A special emphasis is made on magnetic nanoparticle requirements from a physical viewpoint (e.g. relaxivity for MRI and specific absorption rate for hyperthermia), the factors affecting their biodistribution (e.g. size, surface hydrophobic/hydrophilic balance, etc.) and the solutions envisaged for enhancing their half-life in the blood compartment and targeting tumour cells.

http://konsys-t.tanger.cz/files/proceedings/nanocon_11/lists/papers/1094.pdf

Magnetic nanoparticle design for medical diagnosis and therapy

The use of hyperthermia in the treatment of cancers is appealing because, as a physical therapy, hyperthermia would have far fewer restrictive side effects than chemotherapy and radiotherapy, and it could be used in combination with these therapies. However, the currently available modalities of hyperthermia are often limited by their inability to selectively target tumour tissue and, hence, they carry a high risk of collateral organ damage or they deposit heat in a very localized manner which can result in under-treatment of a tumour. Magnetically mediated hyperthermia (MMH) has the potential to address these shortcomings. MMH consists of the localization of magnetic particles or seeds within tumour tissue followed by exposure to an externally applied alternating magnetic field to cause them to heat. Since this concept was introduced (over 40 years ago), MMH has evolved into four general sub-classes: arterial embolization hyperthermia (AEH), direct injection hyperthermia (DIH), intracellular hyperthermia...

https://informahealthcare.com/doi/pdf/10.1080/02656730110108785

Magnetically mediated hyperthermia: current status and future directions

Objective : Ferromagnetic Embolization Hyperthermia (FEH) consists of arterially embolizing tumours with ferromagnetic particles to cause hysteretic heating upon subsequent exposure to an alternating magnetic field. The objective was to determine the effect of tumour size during FEH using a rabbit liver tumour model. Method : Thirty-three rabbits containing implanted hepatic VX2 carcinomas received a hepatic arterial infusion of ferromagnetic particles suspended in lipiodol. Following hysteretic heating, tumour and normal hepatic tissues were chemically analysed for iron content. Tumours were classed as small if their mass was less than the median mass for the whole group of subjects (2.1g), and as large if their mass was greater than or equal to the median. To control for variability in tumour iron concentration, 13 small tumours were matched to 13 large tumours by iron concentration, and their heating characteristics compared. Results : The heating rate in large tumours (median = 5.0°C/min) was signific...

The effect of tumour size on ferromagnetic embolization hyperthermia in a rabbit liver tumour model.

Objective : Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to determine if such particles are cleared from the liver. Method : A lobe of normal liver in three pigs was arterially embolized with 300 mg of &#110 -Fe 2 O 3 particles (150 nm) suspended in lipiodol. The same liver lobe of three other pigs was embolized with 300 mg of ferromagnetic polymer matrix-encapsulated microspheres (32 µm) suspended in 1% tween-water. Samples of liver and blood were obtained before infusion, and at 60 min and 28 days after arterial infusion. At 28 days, samples of lung and other abdominal viscera were also obtained. The tissue samples were chemically analysed for iron content, and submitted to histopathological examination. Results : There was no significant reduction in the hepatic iron concentration in either treatment group 28 days after infu...

Hepatic clearance of arterially infused ferromagnetic particles.

Sirtex Medical Limited is developing new technology to treat liver cancer by induced hyperthermia using magnetic microspheres. Eighty to ninety percent of patients presenting with primary or secondary liver cancer have inoperable disease and a poor prognosis (1-4). The median survival for patients with non-resectable hepatocellular carcinoma is three to six months (5,6), and six to 12 months for patients with non-resectable hepatic colorectal metastases (7). These patients must rely largely on various forms of chemotherapy, radiotherapy and other local or novel treatments. Although these treatments have at times shown promising response rates and symptom palliation and have occasionally down staged hepatic tumours to allow surgical resection, they have not improved five year survival rates which remain in the order of less than 1% (8). The persisting poor survival among the vast majority of patients with hepatic malignancies has stimulated interest in the development of other treatment options, such as targeted hyperthermia. In current clinical practice, hyperthermia therapy is mostly used as an adjunct to radiotherapy in the treatment of superficial and other easily accessible tumour sites. Restrictions to the wider application of hyperthermia to the treatment of tumours located at deep body sites are technological in nature. There are presently no reliable non- invasive techniques that can be used to deliver an adequate heat dose to a localized tumour in a deep body organ such as the liver without risking unacceptable heating of overlying and surrounding normal tissue. The Sirtex technology uses the heat generated in small magnetic microspheres when exposed to a high frequency magnetic field to heat these tumours. It is well known that macroscopic liver tumours derive virtually all their blood supply from the hepatic artery, while normal liver tissue is predominantly supplied by the portal venous system (9). Hence, an infusion of the magnetic microspheres through the hepatic artery results in embolisation of the tumour vasculature with an enhanced concentration of microspheres around any tumours in the liver. This concentration differential ensures only the diseased tissue is heated once the high frequency magnetic field is applied. We have used a rabbit model of liver cancer to investigate different aspects of this new system, including the successful demonstration of tumour heating to therapeutic temperatures with minimal heating of the surrounding parenchyma and the consequent collapse of tumour growth (10). Analysis of the distribution of the magnetic material shows a clear concentration around the edge of the tumour and this is reflected in the measured heating patterns which show the tumour core temperature generally lagging behind that of the tumour rim. This is in direct contrast to the situation in conventional hyperthermia where it is often much easier to heat the necrotic core of a tumour with

S. K. Jones

Papers

Magnetically mediated hyperthermia: current status and future directions

The effect of tumour size on ferromagnetic embolization hyperthermia in a rabbit liver tumour model.

Hepatic clearance of arterially infused ferromagnetic particles.

A system for the treatment of liver cancer by targeted hyperthermia using magnetic microspheres