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[×ÊÔ´] Chemical ReviewsÈȵã×ÛÊö£ºMagnetic Nanoparticles ´ÅÐÔÄÉÃ×Á£×Ó

Magnetic Nanoparticles: Design and Characterization, Toxicity and Biocompatibility, Pharmaceutical and Biomedical Applications

In recent years, considerable e ff orts have been spent in the
development of magnetic nanoparticles (MNPs), the under-
standing of their behavior, and the improvement of their
applicability in many di ff erent areas.
Precise control over the synthesis conditions and surface functionalization of MNPs is
crucial because it governs their physicochemical properties,
their colloidal stability, and their biological behavior/fate. For
pharmaceutical and biomedical purposes, magnetic platforms
should possess very small size and narrow size distribution
together with high magnetization values. Additionally, these
nanoparticles (NPs) must combine high magnetic susceptibility
for an optimum magnetic enrichment and loss of magnetization
after removal of the magnetic fi eld. Finally, their optimal surface
coating is desired in order to ensure tolerance and
biocompatibility, as well as speci fi c localization at the biological
target site. MNPs possessing appropriate physicochemistry and
tailored surface properties have been extensively investigated
for various applications such as drug delivery, hyperthermia,
magnetic resonance imaging (MRI), tissue engineering and
repair, biosensing, biochemical separations, and bioanalysis. In
the fi eld of disease therapy, the development of ¡° theranostics ¡± ,
which facilitates simultaneous drug delivery and imaging,
represents an important breakthrough of MNP technology.
Currently, various clinical trials are in progress to investigate
the potential of di ff erent magnetic nanosystems for pharma-
ceutical and biomedical applications


CONTENTS
1. Introduction 5819
2. Design of Magnetic Colloids 5819
2.1. Synthesis Strategies 5819
2.1.1. Electron Beam Lithography 5819
2.1.2. Gas-Phase Deposition 5819
2.1.3. Sol − Gel Method 5819
2.1.4. Oxidation Method 5820
2.1.5. Chemical Coprecipitation 5820
2.1.6. Hydrothermal Method 5821
2.1.7. Flow Injection Method 5822
2.1.8. Electrochemical Method 5822
2.1.9. Aerosol/Vapor-Phase Method 5822
2.1.10. Sonochemical Decomposition Method 5822
2.1.11. Supercritical Fluid Method 5823
2.1.12. Synthesis Using Nanoreactors 5823
2.1.13. Microbial Method 5823
2.1.14. Synthesis of Metal-Doped Iron Oxide
Nanoparticles 5823
2.2. Stabilization Procedures 5824
2.2.1. Use of Stabilizing Surface Coating
Materials 5824
2.2.2. Encapsulation into Polymeric Shells 5826
2.2.3. Encapsulation into Liposomes 5827
3. Physicochemical Properties and Physicochemical
Characterization 5827
3.1. Geometry 5827
3.2. Structure 5827
3.3. Surface Charge 5828
3.4. Surface Thermodynamics 5828
3.5. Magnetism 5829
3.6. Colloidal Stability 5830
4. Pharmacokinetics, Biodistribution, And Biological
Fate 5830
4.1. In fl uence of the Size 5831
4.2. In fl uence of the Surface Charge 5832
4.3. In fl uence of the Administration Route 5832
4.4. Factors In fl uencing the Tissue/Cell Penetra-
tion 5833
5. Toxicity and Biocompatibility 5834
5.1. In Vitro Evaluation of the Toxicity 5834
5.1.1. In fl uence of the Surface Coatings 5834
5.1.2. In fl uence of the Size 5834
5.1.3. In fl uence of the Surface Charge 5834
5.2. In Vivo Evaluation of the Toxicity 5835
5.2.1. Toxicity after Intravenous Administra-
tion 5835
5.2.2. Toxicity after Intraperitoneal Adminis-
tration 5836
5.2.3. Toxicity after Subcutaneous Administra-
tion 5837
6. Disease Therapy 5837
6.1. Construction of Magnetically Guided Nano-
particles for Drug Delivery 5837
6.2. Chemotherapy 5838
6.2.1. Systemic Chemotherapy 5838
6.2.2. Local Chemotherapy 5842
6.2.3. Oral Delivery 5844
6.2.4. Stimuli-Sensitive Drug Delivery 5844
6.2.5. Miscellaneous Applications 5844
6.3. Magnetofection (Gene Delivery) 5845
6.3.1. In Vitro Magnetofection 5846
6.3.2. In Vivo Magnetofection 5846
6.4. Magnetically Guided Radioimmunotherapy 5847
6.5. Magnetically Guided Photodynamic Therapy 5847
6.6. Magnetic Fluid Hyperthermia 5848
6.6.1. Preclinical Evaluation of Magnetic Fluid
Hyperthermia 5848
6.6.2. Clinical Evaluation of Magnetic Fluid
Hyperthermia 5850
7. Magnetic Resonance Imaging 5850
7.1. Organ/Tissue Imaging 5850
7.1.1. Lymph Node Imaging 5851
7.1.2. Imaging of Atherosclerotic Plaques 5851
7.1.3. Imaging of In fl ammatory Response in
Central Nervous System Disorders 5852
7.1.4. Imaging of Macrophage In fi ltration in
Transplanted Organs 5852
7.1.5. Imaging of Macrophage In fi ltration in
Knee Joints 5853
7.1.6. Imaging Using Ligand-Functionalized
Superparamagnetic Iron Oxide Nano-
particles 5853
8. Cell Labeling and Imaging 5853
8.1. Imaging of Transplanted Stem Cells 5854
8.2. Imaging of Transplanted Pancreatic Islet
Cells 5855
8.3. Imaging of Dendritic Cells 5855
8.4. Imaging of Apoptotic Cells 5855
9. Tissue Engineering 5856
9.1. Engineering of Heterotypic Cell/Tissue Con-
structs 5856
9.2. Sca ff old-Based Tissue Engineering 5856
9.3. Sca ff old-Free Engineering of Three-Dimen-
sional Tissue Constructs 5857
10. Miscellaneous Applications 5857
10.1. Cell Separation and Cell Sensing 5857
10.1.1. Separation of Bacterial Cells And
Mammalian Cells 5858
10.1.2. Separation of Viruses 5859
10.1.3. Magnetic-Relaxation Switches 5859
10.2. Separation of Biochemicals 5859
10.3. Enzyme/Protein Immobilization 5860
10.4. Bioanalysis and Immunoassays 5861
10.5. Separation of Heavy Metal Contaminants
from Mixtures 5863
11. Conclusions 5863
Author Information 5864
Corresponding Author 5864
Notes 5864
Biographies 5864
Acknowledgments 5865
Abbreviations 5865
References 5867Chemical ReviewsÈȵã×ÛÊö£ºMagnetic Nanoparticles ´ÅÐÔÄÉÃ×Á£×Ó
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