Biomedical Applications of Magnetic Particles

Description

Biomedical Applications of Magnetic Particles discusses fundamental magnetic nanoparticle physics and chemistry and explores important biomedical applications and future challenges. The first section presents the fundamentals of the field by explaining the theory of magnetism, describing techniques to synthesize magnetic particles, detailing methods to characterize magnetic particles, and quantitatively describing the applied magnetic forces, torques, and the resultant particle motions. The second section describes the wide range of biomedical applications, including chemical sensors, cellular actuators, drug delivery, magnetic hyperthermia, magnetic resonance imaging contrast enhancement, and toxicity. Additional key features include: Covers both introduction to physics and characterization of magnetic nanoparticles and the state of the art in biomedical applications Authoritative reference for scientists and engineers for all new or old to the field Describes how the size of magnetic nanoparticles affects their magnetic properties, colloidal properties, and biological properties. Written by a team of internationally respected experts, this book provides an up-to-date authoritative reference for scientists and engineers. Cover Half Title Title Page Copyright Page Table of Contents Foreword Preface Editor Bios List of Contributors 1. Introduction to Biomedical Applications of Magnetic Nanoparticles 1.1. Purpose 1.2. Biomedical Applications of Magnetic Particles 1.3. Why Nanoparticles? 1.4. Summary of Subsequent Chapters References Section I: Magnetic Particle Fundamentals 2. A Conceptual Introduction to the Fundamentals of Magnetic Fields, Magnetic Materials, and Magnetic Particles for Biomedical Applications 2.1. Introduction 2.2. Magnetic Fields and Magnetic Moments 2.2.1. Magnetic Flux 2.2.2. Magnetic Moments 2.3. Interaction of Magnetic Materials with Magnetic Fields 2.3.1. Generating Magnetic Fields in the Laboratory 2.3.2. Sample of Material in a Magnetic Field 2.3.3. The B-Field and the H-Field 2.4. Measuring the Magnetic Moment of a Specimen 2.4.1. The Response of the Magnetization of a Material to Magnetic Field Strength, H 2.4.2. Permanent Magnets 2.5. A Microscopic Perspective on Magnetic Materials 2.5.1. Diamagnetism 2.5.2. Paramagnetism 2.5.3. Ferromagnetism 2.5.4. Antiferromagnetism 2.5.5. Ferrimagnetism 2.6. Small-Particle Magnetism 2.6.1. The Stoner-Wohlfarth Particle Model 2.6.2. Magnetic Blocking Temperature 2.6.3. Effects of Applied Magnetic Field on a Single-Domain Particle 2.7. Magnetic Particles in Fluids 2.7.1. Reynolds Number 2.7.2. Interparticle Interactions 2.8. Physical Design Considerations for Magnetic Particles for Specific Applications 2.8.1. Magnetic Carriers 2.8.2. Magnetic Microspheres 2.8.3. Magnetic Hyperthermia 2.8.4. Particles for Brownian Rotation Based Biosensors 2.9. Summary References 3. Magnetic Forces and Torques: Separation, Tweezing, and Materials Assembly in Biology 3.1. Introduction 3.2. Fundamentals of Magnetic Force, Torque, and Dynamics 3.2.1. Magnetic Force and Torque 3.2.2. Dynamics of Particles in Fluids 3.3. Magnetic Separation: Review and Current Trends 3.3.1. Conventional Magnetic Separators 3.3.2. Multiplexed Separation: Linear vs Non-linear Separation 3.4. Biomechanics and Force Spectroscopy 3.4.1. Brief Comparison of SMFS Techniques 3.4.2. Magnetic Tweezers: Recent Results and Current Trends 3.5. Magnetic Assembly: Applications in Microarrays and Tissue Engineering 3.6. Summary Problems References 4. Colloidal Interactions of Magnetic Nanoparticles 4.1. Colloidal Properties of Aqueous Suspensions of Magnetite 4.2. Examples of Stabilized Nanoparticle Systems 4.2.1. Electrostatically Stabilized Magnetite Nanoparticles 4.2.2. Sterically Stabilized Magnetite Nanoparticles 4.2.3. Stabilizing Magnetic Nanoparticles Through the Use of Liposomes 4.2.4. Polyelectrolyte Stabilized Magnetite Nanoparticles 4.3. Mechanisms of Colloidal Instability 4.3.1. Nanoparticle Concentration 4.3.2. Nanoparticle Size 4.3.3. Dissolved Ions in Solution 4.3.4. Polymer Surface Coverage 4.4. Characterization of Colloidal Stability 4.4.1. Thermogravimetric Analysis 4.4.2. Zeta Potential 4.4.3. Scattering Techniques 4.4.3.1 Dynamic Light Scattering 4.4.3.2 Small-Angle X-Ray Scattering 4.4.3.3 Small-Angle Neutron Scattering 4.5. Background on Interparticle Potential Theory Using DLVO Theory 4.5.1. Van der Waals Attractive Forces 4.5.2. Electrostatic Repulsive Force 4.5.3. Extended DLVO Theory 4.5.4. Magnetic Attractive Force 4.5.5. Steric Repulsion 4.5.6. Calculating Colloidal Stability Using Star-Like Polymers 4.5.6.1 Radius of Gyration 4.5.6.2 Calculating the Hydrodynamic Radius 4.6. Summary References 5. Magnetic Characterization: Instruments and Methods 5.1. Introduction 5.2. Instrumentation 5.2.1. DC Magnetometer 5.2.2. Alternating Gradient Force Magnetometer 5.2.3. AC Susceptibility 5.2.4. Mössbauer Spectroscopy 5.2.5. Specialized Techniques 5.2.6. Physical Characterization 5.3. Measurement Methods 5.3.1. DC Hysteresis Loops 5.3.2. Magnetization versus Angle (Torque) 5.3.3. DC Magnetization versus Temperature 5.3.4. Susceptibility versus Field 5.3.5. Susceptibility versus Frequency 5.4. Summary 5.6. Disclaimer 5.5. Acknowledgements Notes References Section II: Magnetic Particle Applications 6. Synthesis and Functionalization of Magnetic Particles 6.1. Introduction 6.2. Materials Choice 6.3. Physical Methods of Nanoparticle Formation 6.3.1. Mechanical Grinding 6.3.2. Metal Evaporation 6.3.3. Sonication 6.4. Chemical Methods of Nanoparticle Formation 6.4.1. The LaMer Mechanism 6.4.2. Ostwald Ripening 6.4.3. Extended LaMer 6.5. Reaction Components 6.5.1. Solvent 6.5.2. Metal Precursor 6.5.3. Surfactant 6.6. Methods to Synthesize Metal Oxide Nanoparticles 6.6.1. Aqueous Precipitation 6.6.2. Hydrothermal Synthesis 6.6.3. Thermolysis in Organic Solvents 6.6.4. Polyol Synthesis 6.7. Methods to Synthesize Metal or Alloy Nanoparticles 6.7.1. Reduction of Salts 6.7.2. Thermolysis/Sonochemical Decomposition 6.8. Purification 6.8.1. Precipitation and Separation 6.8.2. Liquid Chromatography Separation 6.8.3. Hollow Fiber Diafiltration 6.9. Functionalization Strategies 6.9.1. Introduction 6.9.2. Charge Stabilization 6.9.3. Steric Stabilization 6.9.4. Small-Molecule Surface-Bound Monolayers 6.9.5. Small-Molecule Bilayer Coatings 6.9.6. Polymer Coatings by "Grafting to" Approaches 6.9.7. Polymer Coatings by "Grafting from" Approaches 6.9.8. Latex Particle Formation 6.9.9. Silica Coating 6.10. Biofunctionalization 6.11. Summary References 7. Nanomagnetic Actuation: Controlling Cell Behavior with Magnetic Nanoparticles 7.1. Introduction 7.2. Background 7.3. Mechanotransduction in Cells and the Cellular Cytoskeleton 7.4. Magnetic Particles 7.5. Nanomagnetic Actuation for Tissue-Engineering Applications 7.6. Magnetic Activation of Receptor Signaling (MARS) 7.7. Magnetically Actuated Biochips and Cell Patterning 7.8. A Final Thought References 8. Magnetic Nanoparticles: Challenges and Opportunities in Drug Delivery 8.1. Introduction 8.2. Magnetic Nanoparticles (MNPs) 8.3. Conjugation and Release of Drugs from MNPs 8.4. Steps to Drug Delivery 8.4.1. Routes of Administration 8.4.1.1 Oral Delivery 8.4.1.2 Inhalation 8.4.1.3 Transdermal Delivery 8.4.1.4 Direct Injection 8.5. Cellular Internalization of MNPs 8.6. Pharmacokinetics and the Mononuclear Phagocyte System 8.7. Biodistribution of MNPs 8.8. Targeting MNPs to Tumors 8.8.1. Passive Targeting: The Aberrant Physiology of Tumors 8.8.2. Active Targeting of Tumor-Specific Biomarkers 8.8.3. Active Targeting with Magnetic Fields 8.9. Considerations for the Future References 9. Magnetic Particle Biosensors 9.1. Introduction 9.2. Surface Modification 9.3. Magnetic Particle Biosensors 9.3.1. Magnetic Particles as Carriers 9.3.1.1 Electrochemical Detection 9.3.1.2 Chemiluminescent Detection 9.3.1.3 Fluorescent Detection 9.3.1.4 Bio-barcode Detection 9.3.2. Magnetic Particles as Labels 9.3.2.1 Giant Magnetoresistance Detection 9.3.2.2 Single-Particle Detection Methods 9.3.2.3 Magnetic Coil Detection 9.3.2.4 Cantilever Detection 9.3.2.5 SQUID Detection 9.3.2.6 Spin Relaxation Detection with NMR 9.3.3. Dynamics-Based Magnetic Particle Biosensors 9.3.3.1 Single Spherical Magnetic Particles 9.3.3.2 Single Rod-Shaped Magnetic Particles 9.3.3.3 Chains of Magnetic Particles 9.3.3.4 Clusters of Magnetic Particles Acknowledgement References 10. Magnetic Contrast Imaging: Magnetic Nanoparticles as Probes in Living Systems 10.1. Introduction 10.2. Advanced Imaging Applications 10.2.1. Targeted and Molecular Imaging 10.2.2. Quantitative Molecular Imaging 10.2.3. Cellular Tracking 10.2.4. Combined Therapeutic and Diagnostic (Theranostic) Agents 10.3. Magnetic Imaging Technologies 10.3.1. Magnetic Resonance Imaging (MRI) 10.3.2. Magnetomotive Optical Coherence Tomography 10.3.3. Magnetic Particle Imaging (MPI) 10.3.4. Magnetomotive Ultrasound 10.3.5. Other Techniques 10.4. Basic Principles of Magnetic Resonance Imaging 10.4.1. Protons 10.4.2. Applying a Static Magnetic Field 10.4.3. Exciting the Magnetization 10.4.3.1 Longitudinal Relaxation 10.4.3.2 Transverse Relaxation 10.4.3.3 Spin Echo 10.4.4. Generation of Images in MRI 10.4.5. Pulse Sequences and Signal Intensity in MRI 10.5. Contrast Enhancement Mechanisms 10.5.1. R1 Contrast Agents 10.5.1.1 Inner-Sphere Relaxivity 10.5.1.2 Second-Sphere Relaxivity 10.5.1.3 Outer-Sphere Relaxivity 10.5.2. R2 Contrast Agents 10.5.2.1 Static Dephasing 10.5.2.2 Motional Averaging 10.5.2.3 Echo Limiting 10.5.2.4 Relaxivity 10.6. Biocompatibility and Biodistribution 10.7. Existing MRI Contrast Agents 10.7.1. R1 Agents 10.7.2. R2 Agents 10.8. Advanced Contrast Agents 10.8.1. r1 Agents 10.8.2. r2 Agents 10.9. Summary Notes References 11. Energy Dissipation by Magnetic Nanoparticles: Basic Principles for Biomedical Applications 11.1. Examples of Biomedical Applications of Magnetic Nanoparticle Heating 11.1.1. Magnetic Fluid Hyperthermia 11.1.2. Magnetically Triggered Drug Release 11.1.3. Magnetothermal Actuation of Cell Receptors 11.2. Response of Single-Domain Magnetic Nanoparticles to Oscillating Magnetic Fields 11.2.1. Brownian Relaxation by Single-Domain Magnetic Nanoparticles 11.2.2. Néel Relaxation by Single-Domain Magnetic Nanoparticles 11.2.3. Comparison of Brownian and Néel Relaxation Times 11.3. Energy Dissipation by Single-Domain Magnetic Nanoparticles in Oscillating Magnetic Fields 11.3.1. Measurement of Energy Dissipation by Magnetic Nanoparticles--Specific Absorption Rate and Intrinsic Loss Power 11.3.2. Comparison of Brownian and Néel Relaxation Models in Terms of Energy Dissipation 11.3.3. Effect of Particle Size Distribution on Energy Dissipation by Magnetic Nanoparticles 11.4. Practical Limits of Alternating Magnetic Fields for in Vivo Applications 11.5. Summary References 12. Toxicology of Magnetic Nanoparticles 12.1. Introduction 12.2. Introduction to Toxicology 12.2.1. Nanoparticle Disposition 12.2.2. In Vitro Toxicity Testing 12.2.3. In Vivo Toxicity Testing 12.3. Toxicity of Magnetic Nanoparticles 12.3.1. Magnetic Nanoparticle Composition 12.3.2. Cell Culture and Small Animal Studies of Magnetic Nanoparticles 12.3.2.1 Toxicity Studies in Different Cell Lines 12.3.2.1.1 Macrophage Cell Assays 12.3.2.1.2 Fibroblast Cell Assays 12.3.2.1.3 Mesenchymal Stem Cell Assays 12.3.2.1.4 Cancerous Cell Assays 12.3.2.2 Toxicity Studies Regarding Effect of Particle Properties 12.3.2.2.1 Studies with Different Surface Coatings 12.3.2.2.2 Studies with Uncoated SPIONs 12.3.2.2.3 Effect of Particle Surface Charge 12.3.2.2.4 Effect of Particle Size 12.4. Pre-Clinical and Clinical Studies 12.5. Summary References Index