Cover
Title Page
Copyright
Chapter 1: Introduction
1. 1.1 History of Metal Complexes
2. 1.2 Nanotechnology
3. 1.3 Nanoparticles
4. 1.4 Nanotechnology-Supported Metal Nanoparticles
5. Acknowledgment
6. References
Chapter 2: Methods for Preparation of Metal Nanoparticles
1. 2.1 Introduction
2. 2.2 Methods for Preparation of Metallic NPs
3. 2.3 Conclusion
4. References
Chapter 3: Metal Nanoparticles as Therapeutic Agents: A Paradigm Shift in Medicine
1. 3.1 Introduction
2. 3.2 Metal Nanoparticles in Diagnostics
3. 3.3 Advanced Drug Delivery
4. 3.4 Nanoparticle-Mediated Gene Transfer
5. 3.5 Nanotechnology in Regenerative Therapies
6. 3.6 Nanoparticles–Essential Oils Combination Against Human Pathogens
7. 3.7 Conclusion
8. Acknowledgment
9. References
Chapter 4: Nanoparticles for Imaging
1. 4.1 Introduction
2. 4.2 Nanoparticles
3. 4.3 Nanoparticles as Diagnostic Probes
4. 4.4 Nanoparticle-Based Theranostics
5. 4.5 Conclusion
6. References
Chapter 5: Soft-Oxometalates: A New State of Oxometalates and Their Potential Applications as Nanomotors
1. 5.1 Introduction to Soft-Oxometalates (SOMs)
2. 5.2 Application of Soft-Oxometalates
3. 5.3 Active Nano/micro Motors
4. 5.4 Micro-Optomechanical Movement (MOM) in Soft-Oxometalates
5. 5.5 Autonomous Movements Induced in Heptamolybdate SOMs
6. 5.6 SOMs as Water Oxidation Catalysts
7. 5.7 Conclusion
8. Acknowledgment
9. References
Chapter 6: Medicinal Applications of Metal Nanoparticles
1. 6.1 Overview
2. 6.2 Introduction and Background
3. 6.3 Biomedical Applications of Metal Nanoparticles
4. 6.4 Pharmacokinetics of Metal Nanoparticles
5. 6.5 Status of Metal Nanoparticles in Clinical Study
6. 6.6 Future Prospect of Metal Nanoparticles in Medicine
7. Acknowledgment
8. References
Chapter 7: Metal Nanoparticles in Nanomedicine: Advantages and Scope
1. 7.1 Introduction
2. 7.2 Advantages Associated with Metal Nanosystems
3. 7.3 Applications and Scope
4. 7.4 Concluding Remarks
5. Acknowledgments
6. References
Chapter 8: Applications of Metal Nanoparticles in Medicine/Metal Nanoparticles as Anticancer Agents
1. 8.1 Advantages of Metal Nanoparticles
2. 8.2 Metal Nanoparticles as Anticancer Agents
3. 8.3 Gold Nanoparticles
4. 8.4 Silver Nanoparticles (AgNPs)
5. 8.5 Copper Nanoparticles
6. 8.6 Conclusion
7. Acknowledgments
8. References
Chapter 9: Noble Metal Nanoparticles and Their Antimicrobial Properties
1. 9.1 Introduction
2. 9.2 Synthesis of Antibacterial Noble Metal Nanoparticles
3. 9.3 Antibacterial Nanomaterials and Their Antibacterial Mechanism
4. 9.4 Concluding Remarks and Future Outlook
5. References
Chapter 10: Metal Nanoparticles and Their Toxicity
1. 10.1 Introduction to Metal Nanoparticles Toxicity
2. 10.2 Metal Nanoparticle Internalization and Biodistribution
3. 10.3 Physicochemical Properties of Metal Nanoparticles
4. 10.4 Nanoparticle Size and Toxicity
5. 10.5 Nanoparticle Composition and Toxicity
6. 10.6 Nanoparticle Morphology and Toxicity
7. 10.7 Nanoparticle Crystalline Structure and Toxicity
8. 10.8 Nanoparticle Surface and Toxicity
9. 10.9 Nanoparticle Magnetism and Toxicity
10. 10.10 Interaction of Nanoparticles Within Organisms
11. 10.11 Other Novel Properties of Metal Nanoparticles
12. 10.12 Conclusions
13. References
Index
End User License Agreement

List of Illustrations

Chapter 1: Introduction
1. Figure 1.1 Applications of Nanotechnology.
2. Figure 1.2 Various features of engineered nanoparticles.
Chapter 2: Methods for Preparation of Metal Nanoparticles
1. Figure 2.1 Some important examples of physical, chemical, and green sustainable methods for preparation of metallic NPs.
2. Figure 2.2 Some important advantages of using green chemistry methods.
3. Figure 2.3 Advantages and disadvantages of green and biogenic synthesis of metal NPs.
4. Figure 2.4 Advantages of microwave-assisted synthetic approach.
5. Figure 2.5 Some important examples of organisms in metal nanoparticle synthesis.
6. Figure 2.6 Plants in nanoparticle synthesis: the reducing and capping agents.
Chapter 3: Metal Nanoparticles as Therapeutic Agents: A Paradigm Shift in Medicine
1. Figure 3.1 Schematic representation of passive and active targeting of cancer cells by ligand modified nanoparticle-drug complex and nanoparticle-drug complex without ligand.
2. Figure 3.2 Nanoparticulate transfer of genetic material.
Chapter 4: Nanoparticles for Imaging
1. Figure 4.1 Representative examples of nanoparticles (NPs) frequently used for diagnostic and theranostic purposes. USPIO = ultrasmall superparamagnetic iron oxide.
2. Figure 4.2 Blood half-life, extravasation, renal clearance, mononuclear phagocytic system (MPS) uptake, immunologic response, and flexibility to functionalize are important characteristics of imaging probes and theranostic compounds. Diagram illustrates how these properties usually change depending on the probe size. Note that an absolute generalization of probe behavior based on size is not possible, because its composition, surface charge, and functionalization can also have a substantial influence on these properties. * Strongly depends on surface properties of particles. ** Option to increase detection sensitivity by attaching multiple imaging markers/molecule or strong endogenous imaging properties of the particle (e.g., USPIO, microbubble).
3. Figure 4.3 Use of nanoparticles for MPS imaging. (a) MR image shows that liver macrophages strongly incorporate SPIO, leading to decrease in signal intensity of normal liver tissue and improving delineation of hepatocellular carcinoma (arrow). (b) CT scan shows that iodinated polymeric 2-methacryloyloxyethyl(2,3,5-triiodobenzoate) nanoparticles accumulate strongly in liver macrophages, generating positive contrast. Thus, liver metastases in a metastatic mouse model can be differentiated as unenhanced areas (arrows). (c) MR image shows that USPIO nanoparticles can help differentiate metastatic (arrows) and healthy (arrowheads) lymph nodes in patient with tonsillar carcinoma. (d) T2*-weighted MR image of inflammatory lesions after USPIO injection shows that macrophage-rich atherosclerotic plaque (arrow) can be detected owing to its strong decrease in signal intensity.
4. Figure 4.4 Principles of direct labeling methods for cell tracking. For direct labeling of cells, exogenous markers are coupled to either a transfection agent or a positively charged peptide and then incubated with cells. Primary cells, such as lymphocytes, are harvested from a donor first. Once labeled, cells are introduced into the recipient for repeated imaging. Because the label diffuses out of cells and is diluted during cell division, imaging is only feasible over a limited period of time.
5. Figure 4.5 Clinical cell racking. (a–c) MR images obtained before and after injection of dendritic cells labeled with SPIO and ¹¹¹In into patient's lymph node. (a) Gradient-echo transverse image obtained before vaccination shows right inguinal lymph node with high signal intensity (1). (b) Spin-echo transverse image of same lymph node after vaccination. (c) Gradient-echo transverse image obtained after vaccination in same position as in b shows decreased signal intensity in lymph node. 1. (d–n) Images help monitor in vivo migration of labeled dendritic cells 2 days after injection in another patient. (d) Image from in vivo scintigraphy shows migration of dendritic cells from injected lymph node (1) to three additional lymph nodes (2–4). (e–n) Five image pairs (coronal gradient-echo and spin-echo images) show migration of dendritic cells from e,f injection lymph node 1 to g–n, four additional lymph nodes (2–5). Open arrows indicate lymph nodes that do not contain SPIO; solid arrows indicate lymph nodes that are positive for SPIO.
6. Figure 4.6 Labeling implants and grafts. (a) MR image of phantom and (b,c) in vivo MR images of surgical mesh loaded with SPIO nanoparticles. (d) MR image enables noninvasive monitoring of tissue-engineered vascular graft in vivo. Graft was colonized with iron oxide – labeled smooth muscle cells – which facilitated the evaluation of graft location (arrowheads), structure, and function during the 3-week period. * Air in large bowel; ** air in stomach. (e–k) Labeling and multimodal imaging of islet cell-containing microcapsules with different nanoparticles. (e) Schematic of immunoprotective microcapsule loaded with gadolinium–gold nanoparticles, which were clearly visualized on, (f) T1-weighted MR image, (g) T2-weighted MR image, (h) CT scan, and (i) US scan. (j) Fluorine 19 (¹⁸F) MR image hybridized with hydrogen 1 image (gray scale) for highly specific in vivo imaging of perfluorocarbon-containing microcapsules. (k) Chemical exchange saturation transfer–magnetization transfer–weighted overlay show in vivo visualization of cells containing microcapsules labeled with chemical exchange saturation transfer l-arginine liposomes, enabling local sensing of pH changes associated with cell death.
7. Figure 4.7 Nanoparticle-based theranostics. (a) Images show detection of polyvinyl acetate-based contrast agent-labeled microspheres during transcatheter embolization of swine liver. Image in top left is preembolization transcatheter CT angiogram obtained with dilute contrast material. The other images were obtained after transcatheter embolization with 0.2 ml increments of Lipiodol-containing radiopaque microspheres from same catheter tip location within a global branch of hepatic artery. (b) 3D reconstruction of fused MR image and CT scan in patient with glioblastoma treated with magnetic fluid hyperthermia by using Nanotherm depicts primary tumor lesion (brown; MR assessment in upper inset), intratumorally administered magnetic fluid (blue; CT scan in lower inset), and thermometry catheter (green). (c) Gamma camera image of ^99mTc-labeled PEGlated liposomal doxorubicin in patient with Kaposi sarcoma of palmer area of the hand (arrow) demonstrates the potential of using noninvasive imaging techniques to visualize and quantify target site accumulation of nanomedicine formulations. (d) Images of drug targeting to liver with ¹²³l-labeled sugar-modified polymer–drug conjugate show efficient liver localization (left panel: gamma camera image), but inefficient tumor accumulation (upper right panel: SPECT scan shows the distribution of galactosamine-targeted poly-N-[2-hydroxypropyl] methacrylamide–doxorubicin within liver; lower right panel: CT scan of central liver tumor).
Chapter 5: Soft-Oxometalates: A New State of Oxometalates and Their Potential Applications as Nanomotors
1. Figure 5.1 Polyoxometalates that can form SOMs [2].
2. Figure 5.2 (a) Example of spontaneously formed SOMs: [PMo₁₂] peapods observed under TEM Ref. [14]. (Reproduced with permission of American Chemical Society.) (b) Two examples of designed SOMs: Case I: Schematic model showing a gibbsite nanocrystal (left) that is used as a template for forming designed phosphomolybdate Keggin superstructure Ref. [15]. (Reproduced with permission of Royal Society of Chemistry.) Case II: Schematic model of spherical DOTAP template (left) and DOTAP-scaffold designed soft-oxometalate supersphere (right) Ref. [16].
3. Figure 5.3 (A) TEM images of AuNP-SOM (left), SAED pattern (inset), lattice spacing in nanoparticles (right) at ψ = 35. (B) TEM images of AuNP-SOM (a–d), SAED pattern (e), lattice spacing in nanoparticles (f) at ψ = 20. (Adapted from Ref. [28].) (C) Schematic representation of conversion of nanorods to nanospheres (a–c). SEM images (d–f). DLS size distribution plots (g and h). Hydrodynamic radius versus time plot (i) Ref. [29]. (Reproduced with permission of John Wiley & Sons.) (D) SEM images of SD-SOM at different time intervals: At t = 0 (a), at t = 4 h (b), at t = 5 h (c), and at t = 13 h (d) after preparation of dispersion.
4. Figure 5.4 (A) Polystyrene microspheres obtained by varying loading of monomer concentrations (a) 200 µl, (b) 500 µl, (c) 700 µl, and (d) 1000 µl Ref. [28]. (Reproduced with permission of John Wiley & Sons.) (B) SEM images and radii plot of polystyrene nanospheres by varying the ratio of water and DMSO. Points 1–5 refer to the ratios 8.5 : 1.5, 7 : 3, 6 : 4, 5 : 5, and 4 : 6, respectively Ref. [31].
5. Figure 5.5 (A) Schematic of the patterning technique. (B) Pattern “IISER” written with SOM crystals using single bubble on a slide. (C) Schematic representation of phenomenon involved in patterning Ref. [26]. (Panels (A–C) Reproduced with permission of American Chemical Society.) (D) (a) Close-up image of SOM-POF (i). EDX-TEM of SOM-POF (ii). Atomic abundance of different materials present in the dispersion (iii). (b): Time-resolved Raman spectroscopic study showing catalytic oxidation of benzaldehyde using SOM-POF composite as the catalyst and DMSO as the external standard. (c): I_{benzoic acid}/I_DMSO versus time plot confirming formation of benzoic acid.
6. Figure 5.6 (a) SOM peapods as catalyst carrier. AFM images of single peapod (left) and showing topological as well as dimensional changes of [PMo₁₂O₄₀]³-loaded catalyst (right). (b) Controlled motion of an optically trapped particle along the periphery of the ring having diameter 1, 3.5, and 4.5 µm, respectively. (c) Quantified values of particle trajectories as obtained from a commercial software. (d) Catalytic activity of the catalyst as a function of catalyst loading on peapod from spectroscopic analysis.
7. Figure 5.7 (A) Schematic of autonomous movement induced in heptamolybdate SOMs. (B) Time lapse images of moving SOM in 0.014 mol l⁻¹ dithionite. (C) Plot of velocity of SOMs versus concentration of dithionite (left) and trajectories of moving SOM at different dithionite concentrations obtained using commercial tracking software.
8. Figure 5.8 (a) Schematic diagram of water splitting by SOM composite. (b) Comparative oxygen evolution of the SOM composite and the POM alone. (c) Raman spectra of the SOM composite before and after reaction. (d) Catalytic recyclability of the SOM composite catalyst.
Chapter 6: Medicinal Applications of Metal Nanoparticles
1. Scheme 6.1 Representation of application of metal nanoparticles in various biomedical fields.
2. Figure 6.1 (a) Schematic illustration of doxorubicin (DOX)-tethered responsive gold nanoparticles. (b) Schematic illustration of the cooperation between enhanced doxorubicin cellular entry and a responsive intracellular release of doxorubicin into the cells to overcome drug resistance. The fluorescence of doxorubicin tethered to gold nanoparticles is quenched (Fluorescence “OFF”), while recovered when it is released with response to cellular acid conditions (Fluorescence “ON”) Ref. [156].
3. Figure 6.2 Nanocomposite formulation process (a) and NIR laser induced targeted thermo-chemotherapy using the nanocomposite Ref. [47] (b)
4. Figure 6.3 CEA assay with ZnO nanoflowers for in vivo angiogenesis assay. (a, a1) Untreated chicken egg yolks were considered as control; (b, b1) TE (Tris–EDTA) buffer; ZnO nanoflowers at different concentrations (1–20 mg) (c, c1; d, d1; e, e1); and VEGF (10 ng) as positive control experiment (f, f1), respectively. Dose dependent increase of matured blood vessel formation was observed with increasing concentration of ZnO nanoflowers. Black arrows marked indicate the formation of new vasculature. Three angiogenesis parameters were quantified: vessel length (g), vessel size (h), and Junction (i) Ref. [83].
5. Figure 6.4 (a) Redox signaling in angiogenesis by Eu(OH)₃ nanorods in endothelial cells (EC). Generation of ROS, especially H₂O₂ by Eu(OH)₃ nanorods, in the cytosolic part of the EC function as signaling molecules. (b) HUVEC cell proliferation assay. The effect of europium hydroxide [Eu^III(OH)₃] nanorod-induced HUVEC cell proliferation in the presence and absence of MnTBAP (SOD mimetic) and catalase was observed using radioactive [³H]-thymidine, with the results represented as fold stimulation. MnTBAP (10 μM) was incubated with cells in the presence or absence of nanorods and catalase in serum-starved EBM medium. Initially, MnTBAP (10 μM) was incubated with the cells for 15 min, and then, catalase was added and the cells incubated for another 5 min. Finally, Eu^III(OH)₃ nanorods (10 µg ml⁻¹) were added, and the cells incubated for another 24 h. After 24 h, 1 μCi [³H]-thymidine was added into each well. Four hours later, the cells were washed with cold PBS, fixed with 100% cold methanol, and collected for the measurement of trichloroacetic acid precipitable radioactivity. Experiments were performed in triplicate. C, catalase (1200 units ml⁻¹); M, MnTBAP (10 μM); and Eu, Eu^III(OH)₃ (10 µg/ml⁻¹). The data are statistically significant with p ≤ 0.05. The mean ± SD of three separate experiments, each performed in triplicate, was calculated. (c–f) In vivo angiogenesis study in a transgenic FLI-1. EGFP zebrafish model. Nanorods in combination with MnTBAP induce ectopic sprouting from the SIV: lateral view of embryos at 72 hpf. The vehicle control was Tris-EDTA (TE), to which was added 4.5 ng of MnTBAP and/or 50 ng of nanorods. (g) The number of embryos showing normal SIVs, and ectopic sprouting from SIVs is summarized Ref. [84].
6. Figure 6.5 MRI of the polysaccharide biomaterials seeded with 2 million stem cells labeled with the three different doses of GdNPs or seeded with 2 million endothelial cells labeled with IONPs. T2- and T1-weighted sequences were acquired with the same acquisition parameters (described in section “Materials and Methods”). A 3D T1 sequence was also used to allow volume reconstruction. Prior to MRI, the same scaffolds were imaged by confocal microscopy at a four magnification. GdNP1-MSCs were detected in green because of FITC molecules embedded in the silica shell, whereas GdNP2-MSCs were counterstained at the membrane with PKH67 marker. Similarly, the HUVEC-C plasma membrane was stained in red by PKH26 marker. Single cells (circled in white as an example in the confocal imaging zoomed part on the right) appeared densely packed within the pores of the biomaterials Ref. [96].
7. Figure 6.6 In vivo MRI of labeled 9 l cells 24 h after transplantation in the striata of rat brain. (a–c) Spin echo image (TR = 1000 ms, TE = 14.1 ms). (d–f) R1 maps. (g–i) R2 maps. (j–l) R1/R2 mergedmaps. Shown are representative images of three out of seven rats, two injected with MnO- and FeO-labeled cells (a,b), and one with FeO-labeled cells and unlabeled cells (c; control). Note the simultaneous double contrast in (j–l) Ref. [98].
8. Figure 6.7 Effect of apatite-coated TiO₂ suspensions on microbial morphology. (a1 and a2) S. aureus, (b1 and b2) MRSA, (c1 and c2) E. coli, (d1 and d2) M. luteus. Selected SEM images of cell structure show untreated cells (a1–d1) and treated cells with apatite-coated TiO₂ suspensions after black-light activation for 24 h (a2–d2) (×200 000). After treatment with apatite-coated TiO₂ (black arrows), cell morphology changes (white arrows) are seen Ref. [229].
9. Figure 6.8 Study of anti-bacterial activities: (a) liquid growth inhibition kinetics of E. coli using different concentrations of b-AgNPs. b-AgNP-30 (at 30 μM) shows almost 100% growth inhibition. Ampicillin has been used as a positive control (PC) and NC: negative control or untreated E. coli. The numerical number indicates the concentration of b-AgNPs in μM, (b–e) optical images of bacterial colonies formed by E. coli cells, that is, colony counting assay (after 24 h): (b) Control, (c) Ampicillin (100 µg ml⁻¹), (d) b-AgNPs (18 μM), (e) b-AgNPs (30 μM), and (f–h) SEM images of E. coli cells (f) without being treated (control), (g) treated with Olax for 1 h, (h) treated with b-AgNPs (30 μM) for 1 h. The SEM images show the silver nanoparticles damages the bacterial cell membrane (marked by blue arrow), whereas, the bacterial membranes of untreated and treated E. coli with Olax is intact.
Chapter 7: Metal Nanoparticles in Nanomedicine: Advantages and Scope
1. Figure 7.1 (A) Normalized extinction spectra of spherical Ag (38 ± 12 nm diameter), Au (25 ± 5 nm), and Cu (133 ± 23 nm) particles showing their respective LSPR peaks along with the solar spectrum (solar radiation data for air mass 1.5). Contributions from interband transitions are shown as dashed portions in the metal extinction spectra (no surface plasmon resonance in these regions). (Reproduced with permission from Ref. [68] © 2011 Macmillan Publishers Limited.) (B) The tunability of noble metal nanoparticles. Left: Transmission electron micrographs of typical (a) Au nanospheres, (b) Au nanorods, and (c) Ag nanoprisms formed by the citrate reduction, seed growth, and DMF reduction methods, respectively. Right: Photographs showing color variations in the colloidal dispersions of (d) AuAg alloy nanoparticles with increasing Au concentration, (e) Au nanorods of increasing aspect ratio, and (f) Ag nanoprisms with increasing lateral size.
2. Figure 7.2 LSPRs of nonspherical plasmonic nanoparticles. Normalized extinction spectra of Ag wire (90 ± 12 nm diameter and >30 aspect ratio), cube (79 ± 12 nm edge length) and spherical (38 ± 12 nm diameter) nanoparticles Ref. [68].
3. Figure 7.3 FDTD-simulated spatial distribution of the electric field intensity at the LSPR peak wavelength (420 nm) of (a) a 75 nm Ag nanocube and (b) two 75 nm Ag nanocubes separated by a distance of 1 nm and one cube is rotated by 45°. (c) and (d) show the enhancement in the electric field intensity with respect to the incident field at the LSPR peak wavelength as a function of the distance, d, along the dashed lines at the edges of the cubes in (a) and (b), respectively. The field is enhanced and localized at the corners and interparticle junction. Comparison of (c) and (d) shows that the field intensity varies as interparticle junction > corners > edges > surface Ref. [68].
4. Figure 7.4 Glutathione-triggered controlled release of the drug, thiolated doxorubicin (DOX-SH), within cancer cells. Confocal laser scan microscopy images of HeLa cells (a cervical cancer cell line) incubated for 2 h with DOX-SH (bottom row), and DOX-SH-loaded dendrimer-encapsulated gold nanoparticles (G5-OH/Au NPs) (middle and top rows). The cells of the middle row were preincubated with 20 mM GSH-OEt. Left-most column: DOX-SH-loaded G5-OH/Au NPs showed weaker fluorescence as compared to DOX-SH-treated cells. The red fluorescence intensity of DOX in DOX-SH-loaded G5-OH/Au NPs-treated cells is quenched by the Au NPs due to the closeness of DOX to the nanoparticle surface. This shows the slow and sustained release of DOX-SH from the nanoparticles due to the strong Au-S linkage. When the cells were pretreated with GSH-OEt, the fluorescence of the cells treated with DOX-SH-loaded nanoparticles significantly increased. This is attributed to the intracellular GSH-triggered release of the drug, DOX-SH, from the DOX-SH-loaded G5-OH/Au NPs. Second to fourth columns: The nucleus and cytoskeleton of the cells were stained with DAPI (diamidino-2-phenylindole, a blue fluorescent probe) and phalloidin-FITC (green), respectively. It shows that most of the drugs were observed in the nucleus of HeLa cells, suggesting that G5-OH/Au NPs are able to deliver anticancer drugs such as DOX to its active sites in the nucleus Ref. [207].
5. Figure 7.5 Photothermal localized destruction of cells. Left Column: Cells irradiated in the absence of nanoshells maintain both viabilities, as depicted by (a) calcein fluorescence, and membrane integrity, as indicated by the (c) lack of intracellular fluorescein dextran uptake. Cells irradiated in the presence of nanoshells show well-defined circular zones of cell death, as shown by (b) the calcein fluorescence study and (d) cellular uptake of fluorescein dextran resulting from increased membrane permeability Ref. [229].
6. Figure 7.6 Live cell SERS images showing the distributions of gold nanoparticles for their targeted sites such as cytoplasm, mitochondria, or nucleus of HSC-3 cells. Raman images obtained after incubating with subcellular targeting spherical gold nanoparticles with highly narrow intra-nanogap structures (responding to NIR excitation at 785 nm and high-speed confocal Raman microscopy). Three different Raman-active molecules placed in the narrow intra-nanogap showed a strong and uniform Raman intensity in solution even under transient exposure time (10 ms) and low input power of incident laser (200 μW), which led to obtaining high-resolution single cell image within 30 s without inducing significant cell damage. The narrow gap gives high Raman intensity due to “hot-spot” effect. Left column: Cartoons showing gold nanoparticles with various Raman-active molecules placed in the narrow intra-nanogap. Right column: Representative Raman spectra from cells incubated with 4,4′-dipyridyl (44DP)-coded NPs for mitochondria targeting, methylene blue (MB)-coded NPs for cytoplasm targeting, and 4,4′-azobis (pyridine) (AB)-coded NPs for nucleus targeting Ref. [311].
Chapter 8: Applications of Metal Nanoparticles in Medicine/Metal Nanoparticles as Anticancer Agents
1. Figure 8.1 Different metal nanoparticles easily uptook and metabolized by related metal iron transporter.
2. Figure 8.2 The type and biofunction of different metal nanoparticles.
3. Scheme 8.1 Generalized scheme for the biomedical application of AuNPs.
Chapter 10: Metal Nanoparticles and Their Toxicity
1. Figure 10.1 Schematics of the most important physicochemical properties of metal nanoparticles.
2. Figure 10.2 Field emission gun-transmission electron microscopy images of silver nanoparticles that have different sizes: (a) 5 ± 0.7 nm; (b) 7 ± 1.3 nm; (c) 10 ± 2.0 nm; (d) 15 ± 2.3 nm; (e) 20 ± 2.5 nm; (f) 30 ± 5.1 nm; (g) 50 ± 7.1; (h) 63 ± 7.6; (i) 85 ± 8.2; (j) 100 ± 11.2 nm. The upper inset for each image is the high-resolution HRTEM image and lattice fringes (d-spacing). The lower right side shows particle size distribution histograms.
3. Figure 10.3 Scanning and transmission electron microscopic images of gold nanoparticles obtained by laser irradiation at various laser fluences from original octahedral nanoparticles. Laser fluences are (a, b), 1.76 mJ cm⁻² (c, d), 2.87 mJ cm⁻² (e, f), 3.84 mJ cm⁻² (g, h), and 5.50 mJ cm⁻² (i, j) Ref. [71].
4. Figure 10.4 (a) The uptake of gold nanoparticles with various sizes by HeLa cells. (b) Cellular uptake of gold nanoparticles versus the incubation time for gold nanoparticles with diameters of 14, 50, and 74 nm Ref. [27].
5. Figure 10.5 TEM images of nanoparticles with various compositions: (a) Ag, (b) Au, (c) CdS-rich quantum dots, (d) ZnSe rich quantum dots, (e) CuO, (f) TiO₂, (g) ZnO, (h) Fe₂O₃, (i) Fe₃O₄, (j) Al-O, (k) Bi-O, (l) Co-O, (m) Cr-O, (n) In-O, (o) La-O, (p) Mn-O, (q) Ni-O, (r) Sn-O, (s) W-O, (t) Zr-O.
6. Figure 10.6 Composite nanoparticles with different degrees of symmetry, Ag and Al₂O₃ nano-barcodes, Au-TiO₂-Si-Ni nano-zigzags, and Au-Al₂O₃-Cu nanohooks with defined chirality. Upper part shows schematics with structure models while lower part has TEM images Ref. [89].
7. Figure 10.7 Spherical composite nanoparticles. (a) HRTEM image of a Ni particle encapsulated by a graphite shell Ref. [90]. (Reproduced with permission of Elsevier.) (b) Rattle-type Au/CdS composite nanoparticles Ref. [91]. (Reproduced with permission of John Wiley & Sons.) (c, d) TEM images of polymer-coated cobalt nanoparticle chains at different magnifications Ref. [92].
8. Figure 10.8 (a) Cytotoxicity of various metal oxides in cultured A549 cells after exposure to 20 and 40 µg cm⁻² nanoparticles for 18 h. (b) A comparison of cytotoxicity of CuO nanoparticles and Cu ions for increasing concentrations Ref. [85].
9. Figure 10.9 Nanoparticles with different morphologies, with long and short aspect ratio. Transmission and scanning electron microscope images of (a) Au nanowires Ref. [130], (Reproduced with permission of John Wiley & Sons.) (b) Ag nanowires Ref. [131], (Reproduced with permission of Elsevier.) (c) Pd nanotubes, (d) Pd nanosprings (inset shows a drawing of real spring structure) Ref. [128], (Reproduced with permission of American Chemical Society.) (e) Au nanopyramids, and (f) Au nanocubes Ref. [132].
10. Figure 10.10 Nanoparticles made of the same material with various morphologies. TEM images of gold nanoparticles with different shapes: (a–d) nanoplates with triangle, hexagon, pentagon, and so on shape, (e) spherical, (f) urchin shaped. These nanoparticles were synthesized under different reaction conditions by manipulating their growth parameters, such as gold ion concentration, solution pH, and reaction time by using a cell-free extract of the fungal strain Rhizopus oryzae interaction with chloroauric acid. The lower right hand inset for images (b–f) shows selected-area electron diffraction pattern Ref. [130].
11. Figure 10.11 Comparison of the number of gold nanoparticle internalized by HeLa cells as a function of nanoparticle shape. Aspect ratio 1 : 1 denotes spherical nanoparticles, while size is specified at the top of each column in the graph. Aspect ratio of 1 : 3 is for nanoparticles with rod-like morphologies with the length of 40 nm and diameter of 14 nm, while aspect ratio of 1 : 5 is related to gold nanorods with length of 74 nm and diameter of 14 nm Ref. [27].
12. Figure 10.12 (Color online). TEM images of titanium dioxide TiO₂ in (a) anatase and (b) rutile forms. Inset shows schematics of crystalline structure Ref. [136].
13. Figure 10.13 Calculated number of atoms in bulk and on the surface versus nanoparticle size Ref. [138].
14. Figure 10.14 TEM images of human fibroblast cells incubated with gold nanoparticles functionalized with anionic and cationic ligands. Images show increased cellular uptake of cationic bioconjugates. Anionic nanoparticles showed no significant uptake (a, b), while cationic nanoparticles were localized in endocytic vesicles (c, d, e, f) and nucleus (g, h, i, j) Ref. [148].
15. Figure 10.15 (a) Types of magnetic dipoles and their behavior in the absence and presence of external magnetic fields: diamagnetic, paramagnetic, ferromagnetic, ferrimagnetic, antiferromagnetic Ref. [150]. (Reproduced with permission of John Wiley & Sons.) (b) The magnetization of ferromagnetic and superparamagnetic nanoparticles under an external magnetic field; the domains of a ferromagnetic nanoparticle as well as the magnetic moment of single domain superparamagnetic nanoparticle align with the applied field. (Akbarzadeh et al. 2012 [151], https://link.springer.com/article/10.1186/1556-276X-7-144. Licensed under CC BY 2.0.) (c) The magnetization of ferromagnetic and superparamagnetic nanoparticles in the absence of an external magnetic field; the ferromagnetic nanoparticles will have a net magnetization, and superparamagnetic nanoparticles will have no net magnetization due to rapid reversal of the magnetic moment. (d) Schematic illustration of the coercivity versus nanoparticle size and their domain configuration.
16. Figure 10.16 Cell uptake of nanoparticles with their localization in (A). cytoplasm, (B) vacuoles, (C) mitochondrion, and (D) nucleus. Images (a), (b), (c), (d), (e), and (g) represent 5–10 nm silver nanoparticles in TK6 cells. (Huk et al. 2015 [197]. https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-015-0100-x. Licensed under CC BY 4.0.) (f) 40 nm gold nanoparticles in mouse embryonic stem cells. (Sathuluri et al. 2011 [198], http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022802. Licensed under CC BY 4.0.) (h) 4 nm gold nanoparticles in human fibroblast 1BR3G cells Ref. [148]. (Reproduced with permission of American Chemical Society.) The notations in image (f) G, M, L, N, and C represent gold nanoparticle, mitochondria, secondary lysosome, nucleus, and cytoplasm, respectively.
17. Figure 10.17 Environmental scanning electron microscopy (ESEM) images showing nanoparticles in blood of patients with blood diseases. Tissue was collected from explanted vena cava filters in patients with deep-vein thrombosis or pulmonary embolism. The right side of the Figure shows the energy dispersive spectroscopy (EDS) images identifying the composition of nanoparticles entrapped in the tissue. Images show thrombus with nanoparticles of (a) Pb and Cu [37], (b) Fe, Cr, and Ni [37], (c) W and Cu [214], (d) Al, Fe, Cr, and Ni [214].
18. Figure 10.18 The mass percentages of prevalent chemical elements in particles with a coarse, fine and ultrafine size measured in the Shanghai atmosphere during the summer of 2008 Ref. [217].
19. Figure 10.19 Environmental scanning electron microscopy (ESEM) images showing nanoparticles in colon samples of patients with cancer and in thrombi collected from filters in patients affected by blood disorders. The right side of the Figure shows the energy dispersive spectroscopy (EDS) images identifying the composition of nanoparticles entrapped in the tissue. Panel (a) shows nanoparticles of stainless steel in a colon tumor from a young female patient; Panel (b) silver nanoparticles in a colon cancer sample Ref. [61]. (Reproduced with permission of Elsevier.) (c) Silver nanoparticles in ameloblastoma, tumor of odontogenic origin Ref. [65].
20. Figure 10.20 (Color online) Figure 10.17. The absorbance spectra of gold nanoparticles with different aspect ratio. Inset shows TEM images of gold nanoparticles for each absorbance curve Ref. [83].
21. Figure 10.21 (a) The normalized circular dichroism (CD) spectra of left-handed and right-handed gold helices. Inset: TEM images of helices with left (top) and right (bottom) chirality (image dimensions: 85 nm × 120 nm). (b) Schematics of Au nanohelix with two turns showing dimensions Ref. [89].
22. Figure 10.22 (Color online) The variation of melting temperature with nanoparticle size. (a) The melting point, T_m, as a function of nanoparticle size for Ag, Sn, and Pb; Data for the plot were taken from: Ag [238], Sn [239], and Pb [241]. (b) Upper panel: Na clusters with icosahedral growth pattern. Lower panel: Variation of the melting temperature (black), the latent heat of fusion per atom (q, red), and the entropy change (Δs, blue) versus the number of atoms per cluster, N. The three data show maxima around the same N. The cluster sizes are indicated for some peaks Ref. [244].

List of Tables

Chapter 4: Nanoparticles for Imaging
1. Table 4.1 Representative examples for nanoparticle-based imaging probes
Chapter 6: Medicinal Applications of Metal Nanoparticles
1. Table 6.1 List of metal nanoparticles and their biomedical applications
2. Table 6.2 Representative examples of metal nanoparticles and their disease-specific applications
Chapter 7: Metal Nanoparticles in Nanomedicine: Advantages and Scope
1. Table 7.1 Various nanomaterials used in biomedical applications
Chapter 10: Metal Nanoparticles and Their Toxicity
1. Table 10.1 Nanoparticles, their mean aggregate size, particle size, and their relative cytotoxicity index at two concentrations on murine macrophage cells

Metal Nanoparticles

Synthesis and Applications in Pharmaceutical Sciences

Edited by Sreekanth Thota and Debbie C. Crans

Editors

Prof. Sreekanth Thota

Fundação Oswaldo Cruz - Center for Technological Development in Health (CDTS)

Av. Brazil, 4036 - Prédio da Expansão

8 Andar - Sala 814

Manguinhos

Rio de Janeiro 21040-361

Brazil

Prof. Debbie C. Crans

Colorado State University

Department of Chemistry

1872 Campus delivery

United States

Cover Credits: shutterstock/Kateryna Kon

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.d-nb.de.

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-33979-2

ePDF ISBN: 978-3-527-80706-2

ePub ISBN: 978-3-527-80708-6

Mobi ISBN: 978-3-527-80707-9

oBook ISBN: 978-3-527-80709-3

Cover Design Schulz Grafik-Design, Fußgönheim, Germany