Metal Nanoparticles E-Book

• Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 556

Veröffentlichungsjahr: 2018

Beschreibung

A much-needed summary of the importance, synthesis and applications of metal nanoparticles in pharmaceutical sciences, with a focus on gold, silver, copper and platinum nanoparticles. After a brief introduction to the history of metal complexes in medicine and fundamentals of nanotechnology, the chapters continue to describe different methods for preparation of metal nanoparticles. This section is followed by representative presentations of current biomedical applications, such as drug delivery, chemotherapy, and diagnostic imaging.
Aimed at stimulating further research in this field, the book serves as an reference guide for academics and professionals working in the field of chemistry and nanotechnology.

Leseprobe

Table of Contents

Cover

Chapter 1: Introduction

1.1 History of Metal Complexes

1.2 Nanotechnology

1.3 Nanoparticles

1.4 Nanotechnology‐Supported Metal Nanoparticles

Acknowledgment

References

Chapter 2: Methods for Preparation of Metal Nanoparticles

2.1 Introduction

2.2 Methods for Preparation of Metallic NPs

2.3 Conclusion

References

Chapter 3: Metal Nanoparticles as Therapeutic Agents: A Paradigm Shift in Medicine

3.1 Introduction

3.2 Metal Nanoparticles in Diagnostics

3.3 Advanced Drug Delivery

3.4 Nanoparticle‐Mediated Gene Transfer

3.5 Nanotechnology in Regenerative Therapies

3.6 Nanoparticles–Essential Oils Combination Against Human Pathogens

3.7 Conclusion

Acknowledgment

References

Chapter 4: Soft‐Oxometalates: A New State of Oxometalates and Their Potential Applications as Nanomotors

4.1 Introduction to Soft‐Oxometalates (SOMs)

4.2 Application of Soft‐Oxometalates

4.3 Active Nano/micro Motors

4.4 Micro‐Optomechanical Movement (MOM) in Soft‐Oxometalates

4.5 Autonomous Movements Induced in Heptamolybdate SOMs

4.6 SOMs as Water Oxidation Catalysts

4.7 Conclusion

Acknowledgment

References

Chapter 5: Medicinal Applications of Metal Nanoparticles

5.1 Overview

5.2 Introduction and Background

5.3 Biomedical Applications of Metal Nanoparticles

5.4 Pharmacokinetics of Metal Nanoparticles

5.5 Status of Metal Nanoparticles in Clinical Study

5.6 Future Prospect of Metal Nanoparticles in Medicine

Acknowledgment

References

Chapter 6: Metal Nanoparticles in Nanomedicine: Advantages and Scope

6.1 Introduction

6.2 Advantages Associated with Metal Nanosystems

6.3 Applications and Scope

6.4 Concluding Remarks

Acknowledgments

References

Chapter 7: Applications of Metal Nanoparticles in Medicine/Metal Nanoparticles as Anticancer Agents

7.1 Advantages of Metal Nanoparticles

7.2 Metal Nanoparticles as Anticancer Agents

7.3 Gold Nanoparticles

7.4 Silver Nanoparticles (AgNPs)

7.5 Copper Nanoparticles

7.6 Conclusion

Acknowledgments

References

Chapter 8: Noble Metal Nanoparticles and Their Antimicrobial Properties

8.1 Introduction

8.2 Synthesis of Antibacterial Noble Metal Nanoparticles

8.3 Antibacterial Nanomaterials and Their Antibacterial Mechanism

8.4 Concluding Remarks and Future Outlook

References

Chapter 9: Metal Nanoparticles and Their Toxicity

9.1 Introduction to Metal Nanoparticles Toxicity

9.2 Metal Nanoparticle Internalization and Biodistribution

9.3 Physicochemical Properties of Metal Nanoparticles

9.4 Nanoparticle Size and Toxicity

9.5 Nanoparticle Composition and Toxicity

9.6 Nanoparticle Morphology and Toxicity

9.7 Nanoparticle Crystalline Structure and Toxicity

9.8 Nanoparticle Surface and Toxicity

9.9 Nanoparticle Magnetism and Toxicity

9.10 Interaction of Nanoparticles Within Organisms

9.11 Other Novel Properties of Metal Nanoparticles

9.12 Conclusions

References

Index

End User License Agreement

List of Tables

Chapter 5

Table 5.1 List of metal nanoparticles and their biomedical applications.

Table 5.2 Representative examples of metal nanoparticles and their disease‐specific applications.

Chapter 6

Table 6.1 Various nanomaterials used in biomedical applications.

Chapter 9

Table 9.1 Nanoparticles, their mean aggregate size, particle size, and their relative cytotoxicity index at two concentrations on murine macrophage cells.

List of Illustrations

Chapter 1

Figure 1.1 Applications of Nanotechnology.

Figure 1.2 Various features of engineered nanoparticles.

Chapter 2

Figure 2.1 Some important examples of physical, chemical, and green sustainable methods for preparation of metallic NPs.

Figure 2.2 Some important advantages of using green chemistry methods.

Figure 2.3 Advantages and disadvantages of green and biogenic synthesis of metal NPs.

Figure 2.4 Advantages of microwave‐assisted synthetic approach.

Figure 2.5 Some important examples of organisms in metal nanoparticle synthesis.

Figure 2.6 Plants in nanoparticle synthesis: the reducing and capping agents.

Chapter 3

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.

Figure 3.2 Nanoparticulate transfer of genetic material.

Chapter 4

Figure 4.1 Polyoxometalates that can form SOMs [2].

Figure 4.2 (a) Example of spontaneously formed SOMs: [PMo

12

] 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].

Figure 4.3 (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.

Figure 4.4 (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].

Figure 4.5 (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.

Figure 4.6 (a) SOM peapods as catalyst carrier. AFM images of single peapod (left) and showing topological as well as dimensional changes of [PMo

12

O

40

]

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.

Figure 4.7 (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.

Figure 4.8 (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 5

Figure 5.1 Representation of application of metal nanoparticles in various biomedical fields.

Figure 5.1 (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].

Figure 5.2 Nanocomposite formulation process (a) and NIR laser induced targeted thermo‐chemotherapy using the nanocomposite Ref. [47] (b)

Figure 5.3 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].

Figure 5.4 (a) Redox signaling in angiogenesis by Eu(OH)

3

nanorods in endothelial cells (EC). Generation of ROS, especially H

2

O

2

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 [

3

H]‐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 [

3

H]‐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].

Figure 5.5 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].

Figure 5.6

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].

Figure 5.7 Effect of apatite‐coated TiO

2

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 TiO

2

suspensions after black‐light activation for 24 h (a2–d2) (×200 000). After treatment with apatite‐coated TiO

2

(black arrows), cell morphology changes (white arrows) are seen Ref. [229].

Figure 5.8 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 6

Figure 6.1 (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.

Figure 6.2 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].

Figure 6.3 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].

Figure 6.4 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].

Figure 6.5 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].

Figure 6.6 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 7

Figure 7.1 Different metal nanoparticles easily uptook and metabolized by related metal iron transporter.

Figure 7.2 The type and biofunction of different metal nanoparticles.

Figure 7.1 Generalized scheme for the biomedical application of AuNPs.

Chapter 9

Figure 9.1 Schematics of the most important physicochemical properties of metal nanoparticles.

Figure 9.2 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.

Figure 9.3 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].

Figure 9.4 (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].

Figure 9.5 TEM images of nanoparticles with various compositions: (a) Ag, (b) Au, (c) CdS‐rich quantum dots, (d) ZnSe rich quantum dots, (e) CuO, (f) TiO

2

, (g) ZnO, (h) Fe

2

O

3

, (i) Fe

3

O

4

, (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.

Figure 9.6 Composite nanoparticles with different degrees of symmetry, Ag and Al

2

O

3

nano‐barcodes, Au‐TiO

2

‐Si‐Ni nano‐zigzags, and Au‐Al

2

O

3

‐Cu nanohooks with defined chirality. Upper part shows schematics with structure models while lower part has TEM images Ref. [89].

Figure 9.7 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].

Figure 9.8 (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].

Figure 9.9 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].

Figure 9.10 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].

Figure 9.11 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].

Figure 9.12 (Color online). TEM images of titanium dioxide TiO

2

in (a) anatase and (b) rutile forms. Inset shows schematics of crystalline structure Ref. [136].

Figure 9.13 Calculated number of atoms in bulk and on the surface versus nanoparticle size Ref. [138].

Figure 9.14 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].

Figure 9.15 (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.

Figure 9.16 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.

Figure 9.17 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 figures 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].

Figure 9.18 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].

Figure 9.19 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 figures 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].

Figure 9.20 (Color online) Figure 9.17. The absorbance spectra of gold nanoparticles with different aspect ratio. Inset shows TEM images of gold nanoparticles for each absorbance curve Ref. [83].

Figure 9.21 (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].

Figure 9.22 (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 (Δ

s

, 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].

Guide

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Metal Nanoparticles

Synthesis and Applications in Pharmaceutical Sciences

Edited by Sreekanth Thota and Debbie C. Crans

Copyright

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

CO

United States

Cover Credits: shutterstock/Kateryna Kon

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1Introduction

Sreekanth Thota1,2,3 and Debbie C. Crans3

1Fundação Oswaldo Cruz – Ministério da Saúde, National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Av. Brazil 4036 – Prédio da Expansão, 8 Andar – Sala 814, Manguinhos, Rio de Janeiro, 21040‐361, Brazil

2Universidade Federal do Rio de Janeiro, Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Av. Carlos Chagas Filho, Rio de Janeiro, RJ, 21941‐902, Brazil

3Colorado State University, Department of Chemistry, Fort Collins, Colorado, 80523, USA

1.1 History of Metal Complexes

1.1.1 Introduction

Pharmaceutical science, which studies the design, action, delivery, and disposition of drugs, is an important field in drug research. Humans have made several sincere attempts for the search of new drugs in order to cure and control different diseases. Although possible remedial measures are available at present to tackle any disease, scientists are increasingly trying to find superior and more effective drugs [1]. Over the last 50 years some “wonder drugs” have played a crucial role in diminishing the global burden of infectious diseases. New drugs are constantly being screened for their potential biological properties. Among the category of new drugs that are receiving much attention are metal‐based drugs [2]. Precious metals have been used for medicinal purposes for at least 3500 years. Among them, gold has played a crucial role in a variety of medicines in China and Arabia [3].

1.1.2 Metal Complexes

Medicinal inorganic chemistry is in the early days of its development, although there are now a significant number of clinical trials involving metal compounds or other agents that interfere with metabolic pathways for metals, both for therapy and for diagnosis [4]. In chemistry, metal complexes are nothing but reactions between metals and ligands [5]. Biomedical applications of several metal coordination compounds in recent years have provided a substantial contribution to the augmentation of more impressive diagnostic and therapeutic agents [6]. Metal coordination compounds and metal ions are known to effect cellular processes in a dramatic way [7]. Metal coordination complexes offer biological and chemical diversity that is distinct from that of organic drugs.

1.1.3 Metal Complexes in Medicine

In the ancient history of medicine, extraordinarily, many metal‐based drugs played a crucial role as anti‐infective agents. The increasing medicinal application of metals and metal complexes day by day is gaining clinical and commercial significance [8]. The development of metals containing anticancer drugs has been in the 1960s with the synthesis of Platinum compounds. Cisplatin is one of the most extensively used antineoplastic drugs, specifically for the treatment of ovarian and testicular cancers [9, 10]. The success of cisplatin and its analogs has accelerated a resurgence of inorganic medicinal chemistry and the search for complexes of other precious metals [Ru, Va, Zn, Cu, Ag, Gold, Pd] with interesting biological properties [11–17]. Among them, particularly ruthenium compounds have attracted significant attention with two compounds, namely, NAMI‐A and KP1019, advancing through clinical trials [18]. Many precious metals and metal compounds have succeeded in the clinic over the last few decades. Platinum compounds are the most extensively used chemotherapeutic agents, silver compounds have been useful as antimicrobial agents, and gold compounds are used widely in the treatment of rheumatoid arthritis. Scientists have been investigating over the past 25 years several metal‐based compounds and such return of interest in metal‐based drugs can be witnessed in several recent articles [19–24].

1.2 Nanotechnology

1.2.1 Introduction

In today's world, nanotechnology is a relatively new field, but its structural nanometer dimensions and functional devices are not new, and in fact, these materials have much significance. In recent years, we found a plethora of literature explaining the recent advances in nanotechnology [25–33]. Nanotechnology has the potential to provide novel, paradigm‐shifting solutions to medical problems. Nanotechnology, which has been defined as the engineering and manufacturing of materials at the atomic and molecular scale, offers exclusive tools for developing safer and more efficient medicines (nanomedicines), and provides several potential advantages in drug formulation and delivery. Nanotechnology refers to an emerging field of science that includes preparation and development of various nanomaterials. Nowadays, nanomaterials are widely used in many fields including biomedicine, consumer goods, and energy production [34–37]. The purpose of nanomaterials in biotechnology combines the fields of material science and biology.

1.2.2 Development of Nanotechnology

In recent years, disparate products of nanotechnology have played a key role in adding a novel armamentarium of therapeutics to the pipelines of pharmaceutical industries. The nanotechnology fever we are experiencing now began when the United States launched the National Nanotechnology Initiative [38], the world's first program of its kind, in 2000. Nanotechnology usage may possibly achieve many advantages: (i) improved delivery of poorly water‐soluble drugs; (ii) targeted delivery of drugs in a cell‐ or tissue‐specific manner; (iii) drugs transcytosis beyond the tight endothelial and epithelial barriers; (iv) improved delivery of large macromolecule drugs to intracellular sites of action; (v) co‐delivery of multiple drugs or therapeutic modality for combination therapy; (vi) improvement in drug delivery through visualization of sites by combining therapeutic agents with imaging modalities [39]; and (vii) real‐time read on the in vivo efficacy of an agent [40]. Nanotherapeutics has the potential to actively target tumors, increasing the therapeutic effectiveness of a treatment while limiting side effects. This improved therapeutic index is one of the great promises of nanotechnology [41].

1.2.3 Nanotechnology in Medicine

In pharmaceutical trade, a new molecular entity (NME) that exhibits significant biological activity but meager water solubility, or a very terse circulating half‐life, will likely face significant challenges in progress or will be assumed undevelopable [42]. Nanotechnology may revolutionize the rules and possibilities of drug discovery and change the landscape of pharmaceutical industries. In medicine, nanotechnology application may be referred to as nanomedicine that explains various intriguing possibilities in the healthcare sector. The major current and promising applications of nanomedicine include, but are not limited to, drug delivery, in vivo imaging, in vitro diagnostics, biomaterials, therapy techniques, and tissue engineering [28]. In oncology, nanomaterials can enable targeted delivery of imaging agents and therapeutics to cancerous tissues; nanoscale devices enable multiplexed sensing for early disease detection and therapeutic monitoring. The drug delivery field application of nanotechnology is widely expected to change the landscape of pharmaceutical and biotechnology industries in the foreseeable future [40, 43–45]. Nanotechnology attracts scientists because of a wide variety of applications, which includes drugs and medicines, energy, nanoparticles, nanodevices, nanobiotechnology, optical engineering, bioengineering, nanofabrics, and cosmetics (Figure 1.1).

Figure 1.1 Applications of Nanotechnology.

1.3 Nanoparticles

1.3.1 Introduction

Any intentionally produced particle that has a characteristic dimension from 1 to 100 nm and has properties that are not shared by non‐nanoscale particles with the same chemical composition has been called a nanoparticle [46, 47]. Nanoparticles demonstrate a particularly useful platform, describing exclusive properties with potentially wide‐ranging therapeutic applications [48]. The enormous diversity of nanoparticles was described (Figure 1.2). Nanoparticles made of polymers (NPs) are of particular interest as drug delivery systems because of their synthetic versatility as well as their tunable properties (e.g., thermosensitivity and pH response). Nanoparticles offer exciting prospects for improving delivery, cell uptake, and targeting of metallodrugs, especially anticancer drugs, to make them more effective and safer. Transition metal nanoparticles synthesis has been extensively investigated in recent years because of its many unique physical (electronic, magnetic, mechanical, and optical) and chemical properties. Nanoparticles are often in the range 10–100 nm and this is the same size as that of human proteins.

Figure 1.2 Various features of engineered nanoparticles.

1.3.2 Development of Nanoparticles

The primary intention in designing nanoparticles as a delivery system is to manage particle size, surface properties, and release of pharmacologically active agents in order to obtain the site‐specific action of the drug at the therapeutically optimal rate and dose regimen [49]. Nanoscale particles developed using organic molecules as building blocks have been widely examined for drug and gene delivery. For example, polymer, polymersome, and liposome constructs for controlled release of proteins and polymeric micelles, macromolecules, and long‐circulating polymeric nanoparticles are in different stages of clinical and preclinical development [29]. In the 1960s, Bangham and Horne produced the first nanoparticle‐based platform for medical application based on liposomes. In the following decades, nanoparticles gathered more scientific and general interest and developed rapidly [50].

1.3.2.1 Liposome‐Based Nanoparticles

Liposomes are small sphere‐shaped particles, formed by one or more phospholipid bilayers that can be made from cholesterol and natural phospholipids. Depending on the design, they can range from 10 nm up to micrometers [51].

1.3.2.2 Polymeric Nanoparticles

Polymeric nanoparticles might be the most widely used nanoparticle carriers and have been extensively investigated in this regard. They could be formed by biodegradable, biocompatible, and hydrophilic polymers such as poly(D,L‐lactide), poly(lactic acid) (PLA), poly(D,L‐glycolide) (PLG), poly(lactide‐co‐glycolide) (PLGA), and poly‐(cyanoacrylate) (PCA) [52–54].

1.3.2.3 Metal Nanoparticles

Metal nanoparticles are attractive materials in many fields ranging from physics (hard or soft magnetic materials, optics, microelectronics) to catalysis [55]. Noble metal nanoparticles with spherical shape and sharp size distribution such as gold were formed progressively by the chemical reduction method supported by ultrasonic device [56]. The capability to integrate metal nanoparticles into biological systems has had a huge impact in biology and medicine. Some noble metal nanoparticles have been attracting huge interest from the scientific community owing to their awesome properties and diversity of applications, which include gold and silver [57]. The three important properties of gold nanoparticles that have attracted intensive interest are that they are easily prepared, have low toxicity, and readily attach to molecules of biological interest [58].

1.3.3 Nanoparticles in Science and Medicine

Over the past few years nanoparticles have emerged as a key player in modern medicine. Nanoparticles have significance ranging from being contrast agents in medical imaging to being carriers for gene delivery into individual cells [59]. Nanoparticles represent an extraordinarily charming platform for a distinct array of biological significance. In cancer therapy there has been an enormous amount of interest in the preparation and significance of nanoparticles [60]. NPs can easily be conjugated with biomolecules, and thus, they can act as labels for signal amplification in biosensing and biorecognition assays. These strategies can significantly enhance detection sensitivity; even a single molecule can be detected in an ideal case [34]. The exclusive properties and adequacy of nanoparticles emerge from a peculiarity of attributes, including the similar size of nanoparticles and biomolecules such as polynucleic acids and proteins. Additionally, nanoparticles can be formed with a huge range of metal and semiconductor core materials that convey favorable properties such as fluorescence and magnetic behavior [40]. Nanoparticles can afford significant improvements in traditional biological imaging of cells and tissues using fluorescence microscopy as well as in modern magnetic resonance imaging (MRI) of various regions of the body. MRI technique is extensively used in modern medicine, specifically in the diagnosis and treatment of most diseases of the brain, spine, and the musculoskeletal system. Superparamagnetic iron oxide (SPIO) nanoparticles can also be used to visualize features that would not otherwise be detectable by conventional MRI [61]. Several such SPIO nanoparticles have been used in modern MRI [62, 63]. Nanoparticles have already been used for a wide range of applications both in vitro and in vivo. Nowadays various nanoparticles are used in biomedicine. A list of some of the applications of nanomaterials in biology or medicine is given below:

Drug and gene delivery [

64

–

75

]

Fluorescent biological labels [

76

–

80

]

Detection of proteins [

81

]

Biodetection of pathogens [

82

]

Medical imaging [

83

]

Probing of DNA structure [

84

]

Tissue engineering [

85

]

Phagokinetic studies [

86

]

Tumor destruction via heating (hyperthermia) [

87

]

Separation and purification of biological molecules and cells [

88

]

Cancer cell imaging [

89

]

Treatment of cancer [

26

,

69

,

90

,

91

].

Some of the potential applications of nanoparticles are in antibacterial creams and powders (Ag), biolabeling and detection (Au, Ag, quantum dots), bone growth promoters (hypoxyapatite ceramics), cancer diagnostics and targeted drug delivery (magnetic nanoparticles, metal nanoparticles), biocompatible coatings for implants, cell, receptor, antigen, and enzyme imaging (quantum dots), MRI contrast agents (Fe2O3, Fe3O4), gene delivery (CNT), and dental composites [92].

The most widely used nanoparticles in everyday life and in research laboratories are silver nanoparticles (AgNPs). This huge degree of AgNP commercialization has been due to their significant antimicrobial and antifungal properties. Many manufacturers claim that potential AgNP toxicity is minimal or nonexistent. In medical practice silver nanoparticles are commonly used as an integral part of both surgical and nonsurgical equipment such as wound dressings, bandages, and catheters [93].

1.4 Nanotechnology‐Supported Metal Nanoparticles

Drug loading into NPs can be achieved by three techniques: (i) covalent attachment to the polymer backbone, (ii) adsorption to the polymer surface, or (iii) entrapment in the polymer matrix during preparation of the NPs. In most cases metallodrug polymer systems have been formulated by covalent attachment of the metal‐based drug to the polymer backbone. Drug delivery system efficiency can be optimized; for that, carriers must be sufficiently small for the impressive diffusion of the drug‐carrier composite into the targeted cellular environment. Hence, metal nanoparticles, owing to their small size, can be excellent candidates as drug carriers [49, 50]. There has been a great deal of development in the field of gold‐nanoparticle‐mediated cancer therapy in vitro and in vivo in the last 10 years. In recent years, several metal nanoparticles have been widely used [94–107].

Acknowledgment

This work was supported by National Council for Scientific and Technological Development (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Oswaldo Cruz Foundation (Fiocruz).

References

1 Kamatchi, T.S., Chitrapriya, N., Kim, S.K., Fronczek, F.R., and Natarajan, K. (2013) Influence of carboxylic acid functionalities in ruthenium (II) polypyridyl complexes on DNA binding, cytotoxicity and antioxidant activity: Synthesis, structure and in vitro anticancer activity.

Eur. J. Med. Chem.

, 59, 253–264.

2 Kostova, I. (2006) Ruthenium complexes as anticancer agents.

Curr. Med. Chem.

, 13 (9), 1085–1107.

3 Allardyce, C.S. and Dyson, P.J. (2001) Ruthenium in medicine: current clinical uses and future prospects.

Platinum Metals Rev.

, 45 (2), 62–69.

4 Barry, N.P.E. and Sadler, P.J. (2013) Challenges for metals in medicine: How nanotechnology May help to shape the future.

ACS Nano

, 7 (7), 5654–5659.

5 Turel, I. (2015) Practical applications of metal complexes.

Molecules

, 20 (5), 7951–7956.

6 Thota, S., Vallala, S., Yerra, R., and Barreiro, E.J. (2015) Design, synthesis, characterization, cytotoxic and structure activity relationships of novel Ru(II) complexes.

Chin. Chem. Lett.

, 26, 721–726.

7 Reedijk, J. and Bouwman, E. (1999) Metalloenzymes with a quinone co factor.

Bioinorg. Catalysis.

, 12, 563–585.

8 Guo, Z. and Sadler, P.J. (1999) Medicinal inorganic chemisty.

Adv. Inorg. Chem.

, 49, 183–306.

9 Reedijk, J. (1996) Improved understanding in platinum antitumor chemistry.

Chem. Commun.

, 12, 801–806.

10 Wong, E. and Giandomenico, C.M. (1999) Current status of platinum based antitumor drugs.

Chem. Rev.

, 99, 2451–2466.

11 Clarke, M.J. (2003) Ruthenium metallopharmaceuticals.

Coord. Chem. Rev.

, 236, 209–233.

12 Crans, D.C. (2015) Antidiabetic, chemical and physical properties of organic vanadates as presumed transition state inhibitors for phosphatases.

J. Org. Chem.

, 80 (24), 11899–11915.

13 Gao, C.Y., Qiao, X., Ma, Z.Y., Wang, Z.G., Lu, J., Tian, J.L., Xu, J.Y., and Yan, S.P. (2012) Synthesis, characterization, DNA binding and cleavage, BSA interaction and anticancer activity of dinuclear zinc complexes.

Dalton Trans.

, 41, 12220–12232.

14 Santini, C., Pellei, M., Gandin, V., Porchia, M., Tisato, F., and Marzano, C. (2014) Advances in copper complexes as anticancer agents.

Chem. Rev.

, 114 (1), 815–862.

15 Eckhardt, S., Brunetto, P.S., Gagnon, J., Priebe, M., Giese, B., and Fromm, K.M. (2013) Nanobio silver: It's interactions with peptides and bacteria, and its uses in medicine.

Chem. Rev.

, 113 (7), 4708–4754.

16 Shaw III, C.F. (1999) Gold‐based therapeutic agents.

Chem. Rev.

, 99 (9), 2589–2600.

17 Abu‐Surrah, A.S., Al‐Sadoni, H.H., and Abdalla, M.Y. (2008) Palladium‐based chemotherapeutic agents: routes toward complexes with good antitumor activity.

Cancer Therapy.

, 6, 1–10.

18 Rathgeb, A., Bohm, A., Novak, M.S., Gavriluta, A., Domotor, O., Tommasino, J.B., Enyedy, E.A., Shova, S., Meier, S., Jakupec, M.A., Luneau, D., and Arion, V.B. (2014) Ruthenium‐nitrosyl complexes with glycine, l‐alanine, l‐valine,l‐proline, d‐proline, l‐serine, l‐threonine, and l‐tyrosine: synthesis, X‐ray diffraction structures, spectroscopic and electrochemical properties and antiproliferative activity.

Inorg. Chem.

, 53, 2718–2729.

19 Wang, X., Wang, X., and Guo, Z. (2015) Functionalization of platinum complexes for biomedical applications.

Acc. Chem. Res.

, 48 (9), 2622–2631.

20 Simon, P. (2012) Ruthenium compounds as anticancer agents.

Educ. Chem.

, 26–29.

21 Willsky, G.R., Halvorsen, K., Godzala, M.E., Chi, L.H., Most, M.J., Kaszynski, P., Crans, D.C., Goldfine, A.B., and Kostyniak, P.J. (2013) Coordination chemistry may explain pharmacokinetics and clinical response of vanadyl sulfate in type 2 diabetic patients.

Metallomics

, 5 (11), 1491–1502.

22 Crans, D.C., Schoeberl, S., Gaidamauskas, E., Baruah, B., and Roess, D.A. (2011) Antidiabetic vanadium compound and membrane interfaces: interface facilitated metal complex hydrolysis.

J. Biol. Inorg. Chem.

, 16, 961–972.

23 Allardyce, C.S. and Dyson, P.J. (2016) Metal‐based drugs that break the rules.

Dalton Trans.

, 45, 3201–3209.

24 Naggar, M.E., Shehadi, I., Abdou, H.E., and Mohamed, A.A. (2015) Gilded hope for medicine.

Inorganics.

, 3, 139–154.

25 Farokhzad, O.C. and Langer, R. (2009) Impact of nanotechnology on drug delivery.

ACS Nano

, 3 (1), 16–20.

26 Abadeer, N.S. and Murphy, C.J. (2016) Recent progress in cancer thermal therapy using gold nanoparticles.

J. Phys. Chem. C

, 120 (9), 4691–4716.

27 Dreaden, E.C., Alkilany, A.M., Huang, X., Murphy, C.J., and El‐Sayed, M.A. (2012) The golden Age: gold nanoparticles for biomedicine.

Chem. Soc. Rev.

, 2012 (41), 2740–2779.

28 Shi, J., Votruba, A.R., Farokhzad, O.C., and Langer, R. (2010) Nanotechnology in drug delivery and tissue engineering: from discovery to applications.

Nano Lett.

, 10, 3223–3230.

29 Huang, H.C., Barua, S., Sharma, G., Dey, S.K., and Rege, K. (2011) Inorganic nanoparticles for cancer imaging and therapy.

J. Controlled Release

, 155, 344–357.

30 Park, K. (2013) Facing the truth about nanotechnology in drug delivery.

ACS Nano

, 7 (9), 7442–7447.

31 Kratz, F. and Warnecke, A. (2012) Finding the optimal balance: challenges of improving conventional cancer chemotherapy using suitable combinations with nano‐sized drug delivery systems.

J. Controlled Release

, 164, 221–235.

32 Weiss, P.S. (2010) Nanoscience and nanotechnology: present and future.

ACS Nano

, 4 (4), 1771–1772.

33 Goh, D., Tan, A., Farhatnia, Y., Rajadas, J., Alavijesh II, M.S., and Seifalian, A.M. (2013) Nanotechnology‐based gene‐eluting stents.

Mol. Pharmaceutics

, 10, 1279–1298.

34 Benešová, I., Dlabková, K., Zelenák, F., Vaculovič, T., Kanický, V., and Preisler, J. (2016) Direct analysis of gold nanoparticles from dried droplets using substrate‐assisted laser desorption single particle‐ICPMS.

Anal. Chem.

, 88, 2576–2582.

35 Dudkiewicz, A., Tiede, K., Loeschner, K., Jensen, L.H.S., Jensen, E., Wierzbicki, R., Boxall, A.B.A., and Molhave, K. (2011) characterization of nanomaterials in food by electron microscopy.

Trends Anal. Chem.

, 30, 28–43.

36 Martin, C.R. and Mitchell, D.T. (1998) Peer reviewed: Nanomaterials in analytical chemistry.

Anal. Chem.

, 70, 322A–327A.

37 Gowda, S.R., Reddy, A.L.M., Zhan, X., and Ajayan, P.M. (2011) Building energy storage device on a single nanowire.

Nano Lett.

, 11, 3329–3333.

38 The White House Office of the Press Secretary. National Nanotechnology Initiative: Leading to the Next Industrial Revolution. (2000)

http://clinton4.nara.gov/WH/New/html/20000121_4.html

.

39 Liong, M., Lu, J., Kovochich, M., Xia, T., Ruehm, S.G., Nel, A.E., Tamanoi, F., and Zink, J.I. (2008) Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery.

ACS Nano.

, 2, 889–896.

40 Ferrari, M. (2005) Cancer nanotechnology: opportunities and challenges.

Nat. Rev. Cancer

, 5, 161–171.

41 Farrell, D., Alper, J., Ptak, K., Panaro, N.J., Grodzinski, P., and Barker II, A.D. (2008) Recent advances from the national cancer institute alliance for nanotechnology in cancer.

ACS Nano.

, 4 (2), 589–594.

42 Wagner, V., Dullaart, A., Bock, A.K., and Zweck, A. (2006) The emerging nanomedicine landscape.

Nat. Biotechnol.

, 24, 1211–1217.

43 Whitesides, G.M. (2003) The ‘Right’ size in nanobiotechnology.

Nat. Biotechnol.

, 21, 1161–1165.

44 Zhang, L., Gu, F.X., Chan, J.M., Wang, A.Z., Langer, R.S., and Farokhzad, O.C. (2008) Nanoparticles in medicine: therapeutic applications and developments.

Clin. Pharmacol. Ther.

, 83, 761–769.

45 Langer, R. (1990) New methods of drug delivery.

Science.

, 249, 1527–1533.

46 Hansen, S.F., Larsen, B.H., Olsen, S.I., and Baun, A. (2007) Categorization framework to aid hazard identification of nanomaterials.

Nanotoxicology.

, 1, 243–250.

47 Auffan, M., Rose, J., Bottero, J.Y., Lowry, G.V., Jolivet, J.P., and Wiesner, M.R. (2009) Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective.

Nat. Nanotechnol.

, 4, 634–641.

48 De, M., Ghosh, P.S., and Rotello, V.M. (2008) Applications of nanoparticles in biology.

Adv. Mater.

, 20, 4225–4241.

49 Mohanraj, V.J. and Chen, Y. (2006) Nanoparticles – a review.

Tropical Journal of Pharmaceutical Research

, 5 (1), 561–573.

50 Bangham, A.D. and Horne, R.W. (1964) Negative staining of phospho lipids and their structural modification by surface‐active agents as observed in the electron microscope.

J. Mol. Biol.

, 8 (5), 660–668.

51 Torchilin, V.P. (2005) Recent advances with liposomes as pharmaceutical carriers.

Nat. Rev. Drug Discovery

, 4 (2), 145–160.

52 Mundargi, R.C.

et al

. (2008) Nano/Micro technologies for delivering macromolecular therapeutics using poly (D, L‐lactide and co‐glycolide) and its derivatives.

J. Controlled Release

, 125 (3), 193–209.

53 Zhang, K.

et al

. (2014) PEG‐PLGA copolymers: Their structure and structure‐influenced drug delivery applications.

J. Controlled Release

, 183, 77–86.

54 Brannon‐Peppas, L. (1995) Recent advances in the use of biodegradable microparticles and nanoparticles in controlled drug delivery.

Int. J. Pharm.

, 116 (1), 1–9.

55 Costa, N.J.S., Guerrero, M., Colliere, V., Teixeira‐Neto, E., Landers, R., Philippot, K., and Rossi, L.M. (2014) Organometallic preparation of Ni, Pd, and NiPd nanoparticles for the design of supported nanocatalysts.

ACS Catal.

, 4, 1735–1742.

56 Kikuo, Okuyama and Wuled, Lenggoro (2004). Nanoparticle Preparation and Its Application – A Nanotechnology Particle Project in Japan. Proceedings of the 2004 International Conference on MEMS, NANO and Smart Systems (ICMENS'04).

57 Sreeprasad, T.S. and Pradeep, T. (2013)

Noble Metal Nanoparticles

. 303‐388.

58 Giasuddin, A.S.M., Jhuma, K.A., and Mujibul Haq, A.M. (2012) Use of gold nanoparticles in diagnostics, surgery and medicine: a review.

Bangladesh J Med Biochem

, 5 (2), 56–60.

59 Murthy, S.K. (2007) Nanoparticles in modern medicine: state of the art and future challenges.

Int. J. Nanomed.

, 2 (2), 129–141.

60 Zou, L., Wang, H.

et al

. (2016) Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics.

Theranostics.

, 6 (6), 762–772.

61 Mornet, S., Vasseur, S., Grasset, F.

et al

. (2004) Magnetic nanoparticle design for medical diagnosis and therapy.

J. Mater. Chem.

, 14, 2161–75.

62 Huh, Y.M., Jun, Y.W., and Song, H.T.

et al

. (2005) In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals.

J. Am. Chem. Soc.

, 127, 12387–12391.

63 Harisinghani, M.G., Barentsz, J., and Hahn, P.F.

et al

. (2003) Noninvasive detection of clinically occult lymph‐node metastases in prostate cancer.

N. Engl. J. Med.

, 348, 2491–2499.

64 Duncan, R. (2003) The dawning era of polymer therapeutics.

Nat Rev Drug Discov.

, 2, 347–360.

65 Panatarotto, D., Prtidos, C.D., Hoebeke, J., Brown, F., Kramer, E., Briand, J.P., Muller, S., Prato, M., and Bianco, A. (2003) Immunization with peptide‐functionalized carbon nanotubes enhances virus‐specific neutralizing antibody responses.

Chemistry & Biology

, 10, 961–966.

66 Muller, R.H., Mader, K., and Gohla, S. (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art.

Eur. J. Pharm. Biopharm.

, 50, 161–177.

67 Mah, C., Zolotukhin, I., Fraites, T.J., Dobson, J., Batich, C., Byrne, B.

et al

. (2000) Microsphere‐mediated delivery of recombinant AAV vectors in vitro and in vivo.

J. Mol Therapy.

, 1, S239.

68 Torchilin, V.P. and Weissig, V. (eds) (2003)

Liposomes (Practical approach)

, Oxford Univ Press, Oxford.

69 Allen, T.M. and Cullis, P.R. (2004) Drug delivery systems; entering the main stream.

Science

, 303, 1818–1822.

70 Lai, C.Y., Trewyn, B.G., Jeftinija, D.M., Jeftinija, K., Xu, S., Jeftinija, S., and Lin, V.S.Y. (2003) A mesoporous silica nanosphere based carrier system with chemically removable CdS nanoparticle Caps for Stimuli responsive controlled release of neurotransmitters and drug molecules.

J. Am. Chem. Soc.

, 125, 4451–4459.

71 Hong, R., Han, G., Fernandez, J.M., Kim, B.J., Forbes, N.S., and Rotello, V.M. (2006) Glutathione mediated delivery and release using monolayer protected nanoparticle carriers.

J. Am. Chem. Soc.

, 128, 1078–1079.

72 Giri, S., Trewyn, B.G., Stellmaker, M.P., and Lin, V.S.Y. (2005) Stimuli‐responsive controlled‐release delivery system based on mesoporous silica nanorods capped with magnetic nanoparticles.

Angew. Chem. Int. Ed.

, 44, 5038–5044.

73 Polizzi, M.A., Stasko, N.A., and Schoenfisch, M.H. (2007) Water soluble nitric oxide releasing gold nanoparticles.

Langmuir.

, 23, 4938–4943.

74 Yang, Q., Wang, S.H., Fan, P.W., Wang, L.F., Di, Y., Lin, K.F., and Xiao, F.S. (2005) Ph‐Resposive carrier system based on carboxylicacid modified mesoporous silica and polyelectrolyte for Drug delivery.

Chem. Mater.

, 17, 5999–6003.

75 Neuman, D., Ostrowski, A.D., Absalonson, R.O., Strouse, G.F., and Ford, P.C. (2007) Photosensitized NO release from water soluble nanoparticle assemblies.

J. Am. Chem. Soc.

, 129, 4146–4147.

76 Wang, S., Mamedova, N., Kotov, N.A., Chen, W., and Studer, J. (2002) Antigen/antibody immunocomplex from CdTe nanoparticlebioconjugates.

Nano Lett.

, 2, 817–822.

77 Sapsford, K.E., Berti, L., and Medintz, I.L. (2006) Materials for fluorescence resonance enrgy transfer analysis: beyond traditionaldonor‐acceptor combinations.

Angew. Chem. Int. Ed.

, 45, 4562–4589.

78 Bruchez, M., Moronne, M., Gin, P., Weiss, S., and Alivisatos, A.P. (1998) Semiconductor nanocrystals as fluorescent biological labels.

Science

, 281, 2013–2016.

79 Dubertret, B., Calame, M., and Libchaber, A.J. (2001) Single‐mismatch detection using gold quenched fluorescent oligonucleotides.

Nat. Biotechnol.

, 19, 365–370.

80 Keren, K., Berman, R.S., Buchstab, E., Sivan, U., and Braun, E. (2003) DNA‐templated carbon nanotube field‐effect transistor.

Science

, 302, 1380–1382.

81 Nam, J.M., Thaxton, C.S., and Mirkin, C.A. (2003) Nanoparticles‐based bio‐bar codes for the ultrasensitive detection of proteins.

Science.

, 301, 1884–1886.

82 Edelstein, R.L., Tamanaha, C.R., Sheehan, P.E., Miller, M.M., Baselt, D.R., Whitman, L.J., and Colton, R.J. (2000) The BARC biosensor applied to the detection of biological warfare agents.

Biosensors Bioelectron

, 14, 805–813.

83 Medarova, Z., Pham, W., Farrar, C., Petkova, V., and Moore, A. (2007) In vivo imaging of siRNA delivery and silencing tumors.

Nat. Med.

, 13 (3), 372–377.

84 Mahtab, R., Rogers, J.P., and Murphy, C.J. (1995) Protein‐sized quantum dot luminescence can distinguish between “straight”, “bent”, and “kinked” oligonucleotides.

J. Am. Chem. Soc.

, 117, 9099–9100.

85 de la Isla, A., Brostow, W., Bujard, B., Estevez, M., Rodriguez, J.R., Vargas, S., and Castano, V.M. (2003) Nanohybrid scratch resistant coating for teeth and bone viscoelasticity manifested in tribology.

Mat Resr Innovat

, 7, 110–114.

86 Parak, W.J., Boudreau, R., Gros, M.L., Gerion, D., Zanchet, D., Micheel, C.M., Williams, S.C., Alivisatos, A.P., and Larabell, C.A. (2002) Cell motility and metastatic potential studies based on quantum dot imaging of phagokinetic tracks.

Adv. Mater.

, 14, 882–885.

87 Shinkai, M., Yanase, M., Suzuki, M., Honda, H., Wakabayashi, T., Yoshida, J., and Kobayashi, T. (1999) Intracellular hyperthermia for cancer using magnetite cationic liposomes.

J. Magn. Magn. Mater.

, 194, 176–184.

88 Salata, O.V. (2004) Applications of nanoparticles in biology and medicine.

Journal of Nanobiotechnology.

, 2, 1–6.

89 Jain, P.K., Lee, K.S., El‐Sayed, I.H., and El‐Sayed, M.A. (2006) Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: Applications in biological imaging and biomedicine.

J. Phys. Chem. B

, 110 (14), 7238–7248.

90 Johnstone, T.C., Kulak, N., Pridgen, E.M., Farokhzad, O.C., Langer, R., and Lippard, S.J. (2013) Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo Properties.

ACS Nano

, 7 (7), 5675–5683.

91 Ibrahim, N.K., Desai, N., Legha, S.

et al

. (2002) Phase I and pharmacokinetic study of ABI‐007, a cremophor‐free, protein‐stabilized, nanoparticle formulation of paclitaxel.

Clin Cancer Res

, 8, 1038–44.

92 Nagarajan, R. (2008)

Nanoparticles: Building Blocks for Nanotechnology

, ACS Symposium Series, American Chemical Society, Washington, DC.

93 Pantic, I. (2014) Application of silver nanoparticles in experimental physiology and clinical medicine: current status and future prospects.

Rev. Adv. Mater. Sci.

, 37, 15–19.

94 Jain, S., Hirst, D.G., and O'Sullivan, J.M. (2012) Gold nanoparticles as novel agents for cancer therapy.

Br J Radiol.

, 85 (1010), 101–113.

95 Huang, X. and El‐Sayed, M.A. (2010) Gold nanoparticles: optical properties and implementations in cancer diagnosis and photothermal therapy.

J. Adv. Res.

, 1, 13–28.

96 Spivak, M.Y., Bubnov, R.V., Yemets, I.M., Lazrenko, L.M., Tymoshok, N.O., and Ulberg, Z.R. (2013) Gold nanoparticles ‐ the theranostic challenge for PPPM:nanocardiology application.

The EPMA Journal

, 4, 1,1–17.

97 Abou El‐Nour, K.M.M., Eftaiha, A., Al‐Warthan, A., and Ammar, R.A.A. (2010) Synthesis and applications of silver nanoparticles.

Arabian J. Chem.

, 3 (3), 2010.

98 Tran, Q.H., Nguyen, V.Q., and Le, A.T. (2013) Silver nanoparticles: synthesis, properties, toxicology, applications and perspectives.

Adv. Nat. Sci.: Nanosci. Nanotechnol.

, 4 (3), 2013.

99 Mulfinger, L. (2007) Synthesis and study of silver nanoparticles.

J. Chem. Educ.

, 84 (2), 322.

100 Gawande, M.B., Goswami, A., Felpin, F.X., Asefa, T., Huang, X., Silva, R., Zou, X., Zboril, R., and Varma, R.S. (2016) Cu and Cu‐based nanoparticles: synthesis and applications in catalysis.

Chem. Rev.

, 116 (6), 3722–3811.

101 Yang, Y., Sun, C., Ren, Y., Hao, S., and Jiang, D. (2014) New route toward building active ruthenium nanoparticles on ordered mesoporous carbons with extremely high stability. Scientific reports, 4.

102 Maggioni, D., Fenili, F., Alfonso, L.D., Donghi, D., Panigati, M., Zanoni, I., Marzi, R., Manfredi, A., Ferruti, P., Alfonso, G.D., and Ranucci, E. (2012) Luminescent rhenium and ruthenium complexes of an amphoteric poly(amidoamine) functionalized with 1,10‐phenanthroline.

Inorg. Chem.

, 2012 (51), 12776–12788.

103 Cookson, B.J. (2012) The preparation of palladium nanoparticles.

Platinum Metals Rev.

, 56 (2), 83–98.

104 Chen, H., Wei, G., Ispas, A., Hickey, S.G., and Eychumuller, A. (2010) Synthesis of palladium nanoparticles and their applications for surface enhanced raman scattering and electrocatalysis.

J. Physical Chemistry C.

, 114 (50), 21976–21981.

105 Raj, A.T., Ramanujan, K., Thangavel, S., Gopalakrishan, S., Raghavan, N., and Venugopal, G. (2015) Facile synthesis of vanadium‐pentoxide nanoparticles and study on their electrochemical, photocatalytic properties.

J. Nanosci. Nanotechnol.

, 15 (5), 3802–3808.

106 Pinto, S., D'Ornelas, L., and Betancourt, P. (2008) Synthesis and characterization of vanadium nanoparticles on activated carbon and their catalytic activity in thiophene hydrodesulphurization.

Appl. Surf. Sci.

, 254 (17), 5390–5393.

107 Natalio, F., Andre, R., Hartog, A.F., Stoll, B., Jochum, K.P., Wever, R., and Tremel, W. (2013) Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation.

Nat. Nanotechnol.

, 7, 530–535.