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V
Contents
Preface
XIII
List of Contributors
XVII
1 Biofunctionalization of Fluorescent Nanoparticles
1
Michael J. Murcia and Christoph A. Naumann
1.1 Introduction
1
1.2 Fluorescent Nanoparticle Probes
2
1.2.1 Dye-doped Nanoparticles
3
1.2.2 Quantum Dots (QDs)
5
1.2.3 Metal Nanoparticles
7
1.2.4 Hybrid Architectures Involving Fluorescent Nanoprobes
9
1.2.4.1 Metal–Dye
9
1.2.4.2 Dye-doped Silica Shells
9
1.2.4.3 Quantum Dot-containing Microspheres
10
1.3 Bioconjugation of Fluorescent Nanoparticles
11
1.3.1 General Considerations
11
1.3.1.1 Overview
11
1.3.1.2 Common Coupling Reactions
13
1.3.2 Bioconjugation of Polymeric Nanoparticles
13
1.3.2.1 Noncovalent Approaches
13
1.3.2.2 Covalent Approaches
15
1.3.3 Bioconjugation of Quantum Dots
15
1.3.3.1 Noncovalent Approaches
16
1.3.3.2 Covalent Approaches
16
1.3.4 Bioconjugation of Metallic Nanoprobes
16
1.3.4.1 Noncovalent Approaches
17
1.3.4.2 Covalent Approaches
17
1.4 Design of Biocompatible Coatings
17
1.4.1 General Considerations
17
1.4.1.1 Overview
17
1.4.1.2 Colloidal Stability
18
1.4.1.3 Biocompatible Surfaces
19
Nanotechnologies for the Life Sciences Vol. 1
Biofunctionalization of Nanomaterials. Edited by Challa S. S. R. Kumar
Copyright
8
2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
ISBN: 3-527-31381-8
VI
Contents
1.4.1.4 Cytotoxicity
20
1.4.2 Nanoparticle-stabilizing Coatings
21
1.4.3 Low Cytotoxicity Coatings
23
1.5 Applications
23
1.5.1 Biosensing
24
1.5.1.1 Polymeric Sensors
25
1.5.1.2 Quantum Dot Sensors
25
1.5.1.3 Metallic Sensors
26
1.5.2 Fluorescent Nanoparticles as Labels in Biological Imaging
27
1.5.2.1 Dye-doped Nanoparticles
27
1.5.2.2 Quantum Dots
27
References
29
2 Biofunctionalization of Carbon Nanotubes
41
Elena Bekyarova, Robert C. Haddon, and Vladimir Parpura
2.1 Introduction
41
2.2 Carbon Nanotubes – Types, Structures and Properties
42
2.3 Synthesis of Carbon Nanotubes
43
2.4 Approaches to Aqueous Solubilization of Carbon Nanotubes
47
2.4.1 Chemical Modifications
47
2.4.2 Use of Water-compatible Surfactants
47
2.4.3 Functionalization with Water-soluble Polymers
48
2.4.4 Interaction and Functionalization with Biological Molecules
49
2.4.4.1 Noncovalent Biofunctionalization
50
2.4.4.2 Covalent Biofunctionalization
52
2.5 Applications of Biofunctionalized Carbon Nanotubes
54
2.5.1 Assembly of Electronic Devices
54
2.5.2 Biosensing
58
2.5.3 Substrates for Neuronal Growth
63
2.6 Concluding Remarks
65
Acknowledgments
65
References
65
3 Biofunctionalization of Magnetic Nanoparticles
72
Yong Gao
3.1 Introduction
72
3.2 Functionalization of Magnetic Nanoparticles for In Vitro Protein/Cell
Separation
74
3.3 Functionalization of Magnetic Nanoparticles for Biochemical/Chemical
Synthesis of Therapeutic Drugs and Their Intermediates
80
3.4 Functionalization of Magnetic Nanoparticles for In Vivo Bio-imaging,
Drug Targeting and Tumor Hyperthermia Treatments
82
3.4.1 MR Imaging
83
3.4.2 Targeted Drug Delivery
86
3.4.3 Magnetic Hyperthermia
87
Contents
VII
3.5 Conclusions
88
Acknowledgments
89
References
89
4 Biofunctionalization of Gold Nanoparticles
99
Ming Zheng and Xueying Huang
4.1 Introduction
99
4.2 General Synthetic Routes
99
4.2.1 Direct Synthesis of Ligand-protected Au NPs
100
4.2.1.1 Strongly Ionic Ligand-protected Au NPs
102
4.2.1.2 Weakly Ionic Ligand-protected Au NPs
102
4.2.1.3 Au NPs Protected with Neutral Ligands
102
4.2.2 Ligand Exchange Reaction
103
4.3 Preparative-scale Synthesis and Solution-phase Characterization of DNA-
directed Nanoparticle Assemblies
103
4.4 Bifunctional Proteins for Programmable Assembly of
Nanoparticles
111
4.5 Strategies for Eliminating Nonspecific Interactions and Enabling Specific
Binding with Biomolecules
113
4.6 Biological Applications
118
4.6.1 Nucleic Acids
118
4.6.2 Proteins
118
4.6.3 Cells and Virus
119
Acknowledgments
120
References
120
5 Biofunctionalization of Phospholipid Polymer Nanoparticles
125
Junji Watanabe, Jongwon Park, Tomomi Ito, Madoka Takai, and Kazuhiko
Ishihara
5.1 Introduction
125
5.2 Nanofabrication for Biomedical Applications
126
5.2.1 Nano-scaled Processing
126
5.2.2 Key Materials for Nanofabrication
127
5.3 Design of Bioconjugate Nanoparticles
129
5.3.1 Bioconjugate Phospholipid Polymer
129
5.3.2 Solution Properties by Fluorescence Probe
129
5.3.3 Bioconjugate Nanoparticles
131
5.3.4 Surface Elemental Analysis by X-ray Photoelectron Spectroscopy
132
5.3.5 Surface
z
-Potential on Nanoparticles
132
5.3.6 Particle Size by Dynamic Light Scattering and Morphology by Scanning
Electron Microscope
134
5.3.7 Determination of Active Ester Groups on Nanoparticles
135
5.4 Biofunction on Nanoparticles
137
5.4.1 Design of Sequential Enzymatic Reaction
137
5.4.2 Amplified Signal on Nanoparticles
138
VIII
Contents
5.5 Application for Molecular Diagnosis
139
5.5.1 Example of C-reactive Protein Detection Using Nanoparticles
139
5.5.2 High-performance Diagnosis in Serum
143
5.6 Conclusions
145
Acknowledgments
145
References
145
6 Biofunctionalization of Metallic Nanoparticles and Microarrays for
Biomolecular Detection
150
Grit Festag, Uwe Klenz, Thomas Henkel, Andrea Cs
´
ki, and Wolfgang Fritzsche
6.1 Introduction
150
6.1.1 Applications
151
6.1.2 Array Fabrication
151
6.1.3 Detection Methods
153
6.1.3.1 Optical Absorbance
153
6.1.3.2 SPR Imaging
155
6.1.3.3 Raman Scattering
155
6.1.3.4 Electrical Detection
156
6.1.3.5 Electrochemical Detection
156
6.1.3.6 Gravimetric
158
6.2 Nanoparticles and their Biofunctionalization
158
6.2.1 Types of Nanoparticles used for Biomolecular Detection
159
6.2.1.1 Metal Nanoparticles
159
6.2.1.2 Core/Shell Particles
159
6.2.1.3 Magnetic Nanoparticles
160
6.2.1.4 Quantum Dots
160
6.2.2 Synthesis of Gold (Silver) Nanoparticles
161
6.2.3 Biofunctionalization
161
6.2.3.1 Modification of Gold Nanoparticles with Oligonucleotides/DNA
162
6.2.3.2 Modification of Gold Nanoparticles with Proteins
165
6.2.3.3 Biofunctionalization of other Metal Nanoparticles
167
6.2.4 Biological Applications of Gold Nanoparticles
167
6.3 Substrates and their Biofunctionalization
168
6.3.1 Molecular Thin Films
169
6.3.1.1 Self-assembly Monolayers
169
6.3.1.2 Optimization of Gold Nanoparticle-based Microarrays for DNA
Detection
171
6.3.2 Nanoporous Gels
172
6.4 Outlook
175
References
176
7 Conjugation of Nanomaterials with Proteins
183
Mohammed J. Meziani, Yi Lin, and Ya-Ping Sun
7.1 Introduction
183
7.2 Coupling of Inorganic Nanoparticles with Proteins
184
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