reading

Cover
List of Contributors
Series Preface
Preface
1. Structure of This Book
2. Reference
Part 1: Basics of Carbon Nanomaterials
1. 1 Introduction to Carbon Structures
  1. 1.1 Carbon Age
  2. 1.2 Classification
  3. 1.3 Fullerene
  4. 1.4 Carbon Nanotubes
  5. 1.5 Graphene
  6. 1.6 Nanodiamonds and Carbon Dots
  7. Acknowledgment
  8. References
2. 2 Using Polymers to Enhance the Carbon Nanomaterial Biointerface
  1. 2.1 Introduction
  2. 2.2 Colloidal Stability of CNMs
  3. 2.3 Functionalization of CNMs with Polymers
  4. 2.4 Influence of Polymers on the Spectral Properties of CNMs
  5. 2.5 Functionalizing CNMs with Antifouling Polymers for Bioapplications
  6. 2.6 Functionalization of CNMs with Stimuli‐Responsive Polymers
  7. 2.7 Functionalization of CNMs with Polymers for Delivery of Nucleic Acids
  8. 2.8 Outlook
  9. Acknowledgments
  10. References
3. 3 Carbon Nanomaterials for Optical Bioimaging and Phototherapy
  1. 3.1 Introduction
  2. 3.2 Surface Functionalization of Carbon Nanomaterials
  3. 3.3 Carbon Nanomaterials for Optical Imaging
  4. 3.4 Carbon Nanomaterials for Phototherapies of Cancer
  5. 3.5 Conclusions and Outlook
  6. References
Part II: Bioimaging and Bioanalysis
1. 4 High‐Resolution and High‐Contrast Fluorescence Imaging with Carbon Nanomaterials for Preclinical and Clinical Applications
  1. 4.1 Introduction
  2. 4.2 Survey of Carbon Nanomaterials
  3. 4.3 Fluorescent Properties of FNDs and SWCNTs
  4. 4.4 Survey of High‐Resolution and High‐Contrast Imaging
  5. 4.5 Conclusions
  6. References
2. 5 Carbon Nanomaterials for Deep‐Tissue Imaging in the NIR Spectral Window
  1. 5.1 Introduction
  2. 5.2 Carbon Nanomaterials for NIR Imaging
  3. 5.3 Conclusions and Outlook
  4. Acknowledgments
  5. References
3. 6 Tracking Photoluminescent Carbon Nanomaterials in Biological Systems
  1. Chapter Summary
  2. 6.1 Introduction
  3. 6.2 Tracking Cells in Organisms with Fluorescent Nanodiamonds
  4. 6.3 Monitoring Inter and Intra Cellular Dynamics with Fluorescent Nanodiamonds
  5. 6.4 Single‐Walled Carbon Nanotubes: A Near‐Infrared Optical Probe of the Nanoscale Extracellular Space in Live Brain Tissue
  6. 6.5 Conclusion
  7. References
4. 7 Photoacoustic Imaging with Carbon Nanomaterials
  1. Chapter Summary
  2. 7.1 Introduction
  3. 7.2 Photoacoustic Imaging Systems
  4. 7.3 Photoacoustic Application of Carbon Nanomaterials
  5. Acknowledgments
  6. References
5. 8 Carbon Nanomaterial Sensors for Cancer and Disease Diagnosis
  1. 8.1 Introduction
  2. 8.2 Detection of VOC by Using Gas/Vapor Sensors for Cancer and Disease Diagnosis
  3. 8.3 Detection of Biomarkers Using Biosensors for Cancer and Disease Diagnosis
  4. 8.4 Conclusions and Perspectives
  5. Acknowledgments
  6. References
6. 9 Recent Advances in Carbon Dots for Bioanalysis and the Future Perspectives
  1. 9.1 Introduction
  2. 9.2 Fundamentals of CDs
  3. 9.3 Bioengineering of CDs for Bioanalysis
  4. 9.4 Bioanalysis Applications of CDs
  5. 9.5 Future Perspectives
  6. 9.6 Conclusions
  7. References
Part III: Therapy
1. 10 Functionalized Carbon Nanomaterials for Drug Delivery
  1. 10.1 Introduction
  2. 10.2 Direct Fabrication of Graphene‐Based Composite with Photosensitizer for Cancer Phototherapy
  3. 10.3 Polyglycerol‐Functionalized Nanodiamond Conjugated with Platinum‐Based Drug for Cancer Chemotherapy
  4. 10.4 Polyglycerol‐Functionalized Nanodiamond Hybridized with DNA for Gene Therapy
  5. 10.5 Conclusions and Perspectives
  6. Acknowledgments
  7. References
2. 11 Multifunctional Graphene‐Based Nanocomposites for Cancer Diagnosis and Therapy
  1. 11.1 Introduction
  2. 11.2 Multifunctional Graphene‐Based Composites for the Diagnosis/Therapy of Cancer
  3. 11.3 Multimodal Graphene‐Based Composites for the Radiotherapy of Cancer
  4. 11.4 Graphene‐Based Nanobiomaterials for Cancer Diagnosis
  5. 11.5 Conclusion
  6. Acknowledgment
  7. References
3. 12 Carbon Nanomaterials for Photothermal Therapies
  1. 12.1 Introduction
  2. 12.2 GO for PTT
  3. 12.3 CNTs and CNHs for PTT
  4. 12.4 CDs and GDs for PTT
  5. 12.5 Fullerenes for PTT
  6. 12.6 Carbon Nanomaterial‐Based Nanocomposites for PTT
  7. 12.7 Carbon Nanomaterial‐Based Combined Therapy with PTT
  8. 12.8 Conclusions and Perspectives
  9. References
Index
End User License Agreement

List of Tables

Chapter 7
1. Table 7.1 Physical, optical absorption and functional properties of the carbon nanomaterials for photoacoustic imaging contrast enhancement.
2. Table 7.2 Physical, optical absorption, and functional properties of the carbon nanomaterials for photoacoustic (PA) combined multimodal imaging contrast agents. FL, fluorescent; MRI, magnetic resonance imaging.
3. Table 7.3 Physical, optical absorption, and functional properties of the carbon nanomaterials for photoacoustic image‐guided photothermal therapy (PTT) and photodynamic therapy (PDT).
Chapter 9
1. Table 9.1 Some recent examples of CDs prepared from different synthetic strategies and their properties.
Chapter 10
1. Table 10.1 Hydrodynamic diameter and zeta potential of nanoparticles in Milli‐Q water.

List of Illustrations

Chapter 1
1. Figure 1.1 C60 fullerene (or soccer ball) [4].
2. Figure 1.2 SWNT formed from carbon sheet to show unit vectors, chiral vector, chiral index, and angle [10].
3. Figure 1.3 Schematic diagram of three representative SWNT structures in similar diameter: (a) armchair; (b) zigzag; and (c) chiral [11].
4. Figure 1.4 Construction of CNT (5, 2) and band structure of CNT (3, 3) [13].
5. Figure 1.5 Schematic diagram of energy vs. density of states (DOS) for carbon nanomaterials of various dimensions. Occupied electron energy levels (valence band) are shaded and unoccupied levels (conduction band) are white. The first two allowed absorption transitions (E₁₁ and E₂₂) are labeled for the 0D and 1D [14].
6. Figure 1.6 (a) Graphene honeycomb bipartite lattice structure in real space, where the black and white circles denote A‐ and B‐sublattice sites, respectively, a0 is the lattice constant and a = (a, 0) and b = (a/2, 3a/2) are the primitive vectors. The unit cell is indicated by a dotted hexagon. (b) First BZ of graphene. Reciprocal lattice vectors are denoted by a* and b*. K = 2π/a(1/3, 1/√3), K₀ = 2π/a(2/3, 0), Γ = (0, 0). (c) π‐band structure of graphene along Γ‐M‐K‐Γ within the irreducible BZ. γ₀ is the transfer integral between nearest‐neighbor carbon sites (γ₀ = 3.16 eV). (d) Density of states (DOS) of the π band. (e) Three dimensional π‐band structure of graphene near the K point. Pseudospin is indicated by an arrow [20].
Chapter 2
1. Figure 2.1 Colloidal interactions of NPs. (a) At the most basic level, NP aggregation is governed by van der Waals interactions. Permanent or induced dipoles within the NP can result in net attractive forces between NPs and subsequent aggregation. (b) Macromolecules can physically stabilize NPs. Hydrophilic macromolecules can shield the NPs from interactions, and steric stabilization can be combined with charge stabilization for electro‐steric stabilization. (c) The inherent surface charge of NPs, caused by surface ions or functional groups, results in formation of the stern layer, oppositely charged ions adsorbed to the NP surface. Ions with an opposite charge from the stern layer form the diffuse layer. Together, this is referred to as the electric double layer (EDL). The EDL forms a net charge, and when two like particles are in proximity, the EDL repels the two. (d) Illustration of potential energy (ψ) distance (d) curves. They can be used to predict the contribution of the different stabilization approaches and model the stability of NPs in solution.
2. Figure 2.2 (a) Band diagram of a semiconducting SWCNT, showing fluorescence emission after excitation. (b) A NIR photoluminescence spectrum of a SWCNT. (c) Photoluminescence spectra of single NV⁻ and NV⁰ color centers in nanodiamonds. The zero‐phonon lines of NV⁻ and NV⁰ are indicated with ⋆ symbols; the emissions are located at 637 and 575 nm, respectively. The inset shows the atomic structure of the NV defect, consisting of a substitutional nitrogen atom (N) associated to a vacancy (V) in an adjacent lattice site of the diamond crystalline matrix.
3. Figure 2.3 (a) In serum‐containing media, nanoparticles are covered with proteins (protein corona), which leads to interaction of the nanoparticles with cells and their subsequent internalization. (b) A dense polymeric shell makes nanoparticles resistant to protein adsorption and cell interaction.
4. Figure 2.4 (a) Schematic structure of HPHT nanodiamonds with NV centers coated with a thin layer of silica and poly[N‐(2‐hydroxypropyl)methacrylamide] layer modified with cyclic RGD and the secondary fluorescent label Alexa fluor 488. (b) Fluorescence intensity measurement of U87‐MG glioblastoma cells incubated with: nanodiamonds bearing cyclic RGD (FND‐cRGD) with (cRGD+) or without preincubation with free cyclic RGD; nanodiamonds with polymeric shell without RGD modification (FND) with (cRGD+) or without preincubation.
5. Figure 2.5 (a) Schematic illustration of the pH dependence of the interaction mode for graphene/PAA particles and (b) Dynamic light scattering (DLS) histograms of graphene/PAA solution (1 : 10) at different pH.
6. Figure 2.6 Various CNM surface functionalizations for gene delivery. (a) Noncovalent functionalization of SWCNTs with PL‐PEG‐NH₂ for conjugation of thiol–siRNA through disulfide linkages. (b) Covalently attached PEI on SWCNTs obtained by cationic polymerization of aziridine. (c) Noncovalent PEI grafting based on electrostatic interaction used for pDNA delivery. (d) “Grafting from” method using ATRP to construct polycation‐functionalized nanodiamonds (DND/PDMAEMA). (e) GO noncovalently functionalized with PEI polymers, forming positively charged GO‐PEI complexes. (f) Branched PEI‐functionalized CDs condensed with DNA by electrostatic interaction. (g) The synthetic route to CDs, CD‐Br, and CD‐polymers.
Chapter 3
1. Figure 3.1 Carbon nanomaterials including fullerene, carbon nanotube, graphene, carbon dot, and nanodiamond.
2. Figure 3.2 Noninvasive photoluminescent (635/710) imaging of nude mice harboring HCT‐116 or KB tumors. HA‐F1 was intravenously injected into tumor‐bearing nude mice. Photoluminescent images were obtained for four hours after injection. Tumors are indicated by the white arrows. (See color plate section for the color representation of this figure.)
3. Figure 3.3 (a) Cellular imaging of GQDs under 405 and 488 nm excitation, respectively; (b) Representative two‐photon luminescence image (800 nm excitation) of human breast cancer MCF‐7 cells with internalized CDs. (See color plate section for the color representation of this figure.)
4. Figure 3.4 (a, b) Subcellular distribution of CNT complexes in PC3 cells. Cells were incubated with 30 g ml⁻¹ of oxDWNT‐RNA‐FS for two hours; (c–e) SWNT NIR emission showing accumulation in the dorsal vessel. Green fluorescence from green fluorescent protein (GFP) expressed exclusively in the dorsal vessel is shown in panel (c), and NIR fluorescence from nanotubes is shown in panel (d) (false colored in red). (e) Overlay of these two images on the corresponding bright field image, demonstrating that the SWNTs lie within the lumen of the vessel. Scale bars are 25 μm. NIR photoluminescence images of nude mice treated with 200 μl of 17 mg ml⁻¹ exchange‐SWNTs (f) and 200 μl of 260 mg ml⁻¹ direct‐SWNTs (g). (See color plate section for the color representation of this figure.)
5. Figure 3.5 Differential interference contrast (DIC) and stacked confocal fluorescence images of bovine serum albumin (BSA)‐conjugated fluorescent nanodiamonds (FNDs) in zebrafish embryos at 4.7 hpf (a) and ~60 hpf (b). The corresponding control experiments were performed without FND injection to the zebrafish embryos. The developmental ages are 4.3 hpf (c) and ~60 hpf (d), respectively. (See color plate section for the color representation of this figure.)
6. Figure 3.6 Spectrally unmixed in vivo fluorescence images of 4T1 tumor‐bearing Balb/c mice, KB, and U87MG tumor‐bearing nude mice at different time points post injection of NGS‐PEG‐Cy7. Mouse autofluorescence was removed by spectral unmixing in the above images. High tumor uptake of NGSPEG‐Cy7 was observed for all of the three tumor models. Hairs on Balb/c mice were removed before fluorescence imaging.
7. Figure 3.7 (a) Representative photos of tumors on mice after various treatments indicated. The laser‐irradiated tumor on the nanographene sheet (NGS)‐injected mouse was completely destructed; (b) Thermal images of vials containing pellets of control nontreated U87MG cells, cells treated by nano‐rGO‐RGD, and cells treated by nano‐rGO‐RAD, respectively, after eight minutes of irradiation with an 808 nm laser at a power of 15.3 W cm⁻² . (See color plate section for the color representation of this figure.)
8. Figure 3.8 Dose‐dependent PDT effects of the cell viability of HeLa cells: (a) GQDs in the concentration range 0.036–1.8 μM; (b) PpIX in the concentration range 0.36–18 μM; (c) Photographs of mice after various treatments on the 1st, 9th, 17th, and 25th day. (PDT: GQDs þ light irradiation; C1: GQDs only; C2: light irradiation only.)
Chapter 4
1. Figure 4.1 Functionalization of FNDs. (a) Nanodiamonds in tetraethyl orthosilicate (TEOS) are trapped in multilaminar vesicles (MLVs) of phospholipid Palmitoyloleoyl‐oleoyl‐phosphatidylcholine (POPC) with the size range 500–10 000 nm. MLVs are broken by ultrasonication into small unilaminar vesicles (SUVs) of nominally ~100 nm diameter. The conversion of TEOS into silica is catalyzed by triethylamine (TEA). Free TEOS and TEA are dialyzed and followed by an SDS wash to break up the liposomes. SDS and POPC are removed by dialysis to obtain the silica‐coated diamonds. The final product is stabilized and monodispersed silica‐encapsulated nanodiamonds. (b) The silica‐encapsulated FNDs have free silanol groups that can be used to attach desired ligand using a variety of silane agents. Adapted with permission from Bumb et al. [6]. (See color plate section for the color representation of this figure.)
2. Figure 4.2 Properties of FNDs. (a) Schematic of a nitrogen vacancy defect in diamond lattice. (b) Simplified energy level diagram of the ground and first excited state of NV¯ centers. The dashed lines denote nonradiative transitions. (c) Image of a large number of 100 nm FNDs fixed to a glass slide. (d) Fluorescence intensities of a single AlexaFluor555 dye (red) and a 100 nm FND (blue). (e) Normalized histogram (blue bar) and Gaussian fit (black line) of the average intensity of a typical FND from the image shown in (c). The data was taken in 1 s intervals over the course of 45 min. The dashed red lines denote the 95% confidence bounds. (f) Photoluminescence excitation spectrum (blue) and photoluminescence emission spectrum (red) of 100 nm FNDs. The shaded regions denote the standard deviations. (See color plate section for the color representation of this figure.)
3. Figure 4.3 Background‐free imaging via magnetic modulation of FND emission. (a) An example of intensity modulation of an FND upon application of ~100 G magnetic field with 0.1 Hz square wave (0–100 G amplitude) modulation. (b) A field of view with ~40 nm FNDs containing ~15 NV– centers imaged with a total internal reflection fluorescence microscope (TIRFM). (c) Image of the same field of view after introducing ~1 μM Alexa647 dye solution into the sample chamber to introduce high background. (d) The mean (Image_OFF − Image_ON) for 1000 pairs of images similar to the image in (b). (e) Image of a mouse with background (top left), the mean (Image_OFF − Image_ON) of 475 pairs of images (bottom left), and the combined overlaid image (right), where the bottom white arrow is the injection site in the footpad and the top white arrow is the location of auxiliary lymph node. (f) The combined image of open chest cavity of the same mouse in (e) with two different types of image processing: the mean (Image_OFF − Image_ON) (left) and the phase sensitive pixel‐by‐pixel lock‐in processing (right). The white arrows point to the injection site and the location of auxiliary lymph node. (g) The pixel values as a function time corresponding to the selected points in (e) and (f) to show signal modulation as a result of the applied magnetic field. (See color plate section for the color representation of this figure.)
Chapter 5
1. Figure 5.1 Optical windows in biological tissues. Plots of effective attenuation coefficient (on a log scale) versus wavelength show that absorption and scattering from oxygenated blood, deoxygenated blood, skin, and fatty tissue is lowest in either the first or second near‐infrared window [3, 4].
2. Figure 5.2 Members of the carbon nanomaterial family.
3. Figure 5.3 Fullerene‐oligothiophene chromophores structure (left); Open‐cage strategy for improving fullerene absorbance (right).
4. Figure 5.4 Schematic density of electronic states for a single nanotube structure illustrating the transitions leading to SWCNT fluorescence. Solid arrows depict the optical excitation and emission transitions of interest.
5. Figure 5.5 Noninvasive imaging of ovarian tumors using SBP–M13 conjugated to SWNTs (NIR‐II), AlexaFluor750 (NIR‐I), and FITC (Visible) (top to bottom). Arrows in the SWNT panel denote nodules visible only by SWNTs (n = 3 animals). (See color plate section for the color representation of this figure.)
6. Figure 5.6 (a) A C57Bl/6 mouse head with hair removed. (b–d) Fluorescence images of the same mouse head in the NIR‐I, NIR‐II, and NIR‐IIa regions. In (d), the inferior cerebral vein, superior sagittal sinus and transverse sinus are labeled 1, 2, and 3, respectively. (e) Extinction spectra of scalp (red) and skull (blue) as well as the water absorption spectrum (black). (f) Reduced scattering coefficients μ of scalp skin (red), cranial bone (blue), and brain tissue (black) plotted against wavelength. (See color plate section for the color representation of this figure.)
7. Figure 5.7 (a) AFM (left), HRTEM (center), and confocal microscopy (right) images of azaBODIPY‐CNO (red color), internalized in HeLa Kyoto cells in the case of the confocal microscopy image. (b) 3D Laser confocal microscopy z‐stacking image of fluorescent CNOs aggregates deposited on polystyrene, which illustrates the intense red fluorescence of the BODIPY‐functionalized CNOs. Excitation at 647 nm; detection of the fluorescence in a range of 700 ± 35 nm. (See color plate section for the color representation of this figure.)
Chapter 6
1. Figure 6.1 Identification of transplanted FND‐labeled lung stem cells in bronchiolar epithelia and their histomorphometric distribution. (a) Lung tissue sections prepared from naphthalene‐injured mice on day 7 after intravenous injection of FND‐labeled LSCs. (b) left: immunostaining (brown) of club cells with via the targeting of CCSP (club cell secretory protein) marker. The enlarged images in the red dashed boxes show FLIM (red color correspond to ≈20 ns fluorescence lifetime, and green to ≈2 ns) in the middle, and (a), right: merge of anti‐CCSP and time‐gating fluorescence (red) signals. FND‐labeled LSCs (red) co‐localize with CCSP⁺ (brown) cells and reside at the bronchiolar epithelial region of the lung. Scale bar: 10 μm. (b) Histomorphometric distribution measured by visually counting the numbers of FND‐labeled LSCs nested in terminal bronchioles (black) or alveoli (white) of the lungs of uninjured and injured mice on day 7 after intravenous injection. Results are averages of more than 30 visual fields per section, with error bars representing standard deviations of the measurements (n = 6 per group). (See color plate section for the color representation of this figure.)
2. Figure 6.2 In vivo imaging and tracking of FND‐labeled cancer cells in mouse ear blood vessels, after intravenous injection. (a) Photograph of the experimental arrangement. (b) Bright‐field image of a mouse ear tissue (no time‐gating). The green arrow indicates the position of an FND‐labeled lung cancer cell in the blood vessel of ≈50 μm in diameter. (c) Enlarged view of (b) fluorescence image, in time‐gated mode, and after subtraction of stationary autofluorescence background, showing one bright spot which corresponds to an FND‐labeled lung cancer cell. (d) Enlarged view of (c) time‐gated fluorescence image, showing the trajectory of the FND‐labeled cell in the vessel.
3. Figure 6.3 Tracking protein conjugated‐FND in C‐elegans worm and drosophila embryo. (a1) Superposition of bright‐field and time‐gated fluorescence image of a representative C‐elegans worm at 55 minutes after injection of GFP::YLC‐FND into the intestinal cell. The blue arrow indicates the injection site. Scale bars: 50 μm. (a2) An enlarged image (left) and a cartoon (right) of the area in the red box in (a1), showing the presence of GFP::YLC‐FND in both intestine (left: yellow dotted line for the boundary; right: “in”) and oocytes (left: thin white lines and nuclei labeled with blue stars; right: “oo”). (b1) Scanning confocal fluorescence image of individual nanodiamonds in the blastoderm cells during stage 5 of development of a drosophila embryo. The image shows the auto‐fluorescence from the junction of each blastoderm cell as well as the strong fluorescent signal from individual nanodiamonds which in the majority of cases is localized to the cell periphery. (b2) Schematic of the micro‐injection of nanodiamonds into the drosophila embryo. Embryos at early (left) and late (c) stage 5 showing the cellularization furrows introgressing between nuclei, which invade the yolk‐free periplasm during the later syncytial divisions (right, arrows). The ingressing membranes eventually join and pinch off individual blastoderm cells, forming a large, internal yolk cell. Nanodiamonds that have diffused into the yolk‐free periplasm can become internalized in the blastoderm cells at the completion of stage 5.
4. Figure 6.4 Intracellular tracking of single FND, one cell at a time. (a) 3D‐tracking of a single 35‐nm FND in a live HeLa cell. Left: overlay of bright‐field and red epifluorescence images of the cell after FND uptake. Middle: 3D‐reconstruction showing the nucleus and cytoplasm of the cell, as well as the red spot of the internalized FND. Right: 3D‐trajectory reconstruction of a single FND (surrounded by a yellow box in a) inside the cell over a time span of 200 seconds. (b) Single‐particle tracking of TGF‐β membrane receptors labeled with TGF‐conjugated FND in living cancer cell line. (b1) Left: TGF‐β trajectories overlaid with wide‐field fluorescence images without SMI treatment. Color corresponds to the track numbers. Scale bar: 3 μm. Right: distribution of the anomalous diffusion parameter α, showing three prominent peaks corresponding to the three different diffusion regimes (peaks from left to right: immobile, anomalous, and Brownian). (b2) Same as (b1) but with SMI treatment of cancer cell culture. Note that the fraction of immobile particles decreases substantially. (See color plate section for the color representation of this figure.)
5. Figure 6.5 Single FND tracking inside branches of neuron reveals intraneuronal transport abnormalities. (a) Left: bright‐field image merged with the FND red channel showing four FND moving inside neuronal branches (yellow arrows). The FND‐containing endosomes labeled #1 and #2 (solid white line box) were observed moving in the same branch and toward the cell soma (not visible in this image). Scale bars: 5 μm. Right: snapshot at different time of the two FND emphasizing their trajectory (yellow and green respectively; from white box in (a), left). Scale bars: 1 μm. (b) Top: trajectories of FND #1 and #2 extracted from dashed line rectangle in (a, right). The two colors in each trajectory correspond to “go” phases (in green for FND #1 and yellow for FND #2) and “stop” phases (in blue for FND #1 and red for FND #2). Bottom: two‐state (“stop” and “go”) representation of the same trajectories over time: FND #1 moved faster than FND #2 (scale bar: 1 second). (c) application of the FND‐tracking assay to Alzheimer's disease model. Aβ_1–42 used at concentrations of 0.5 μM (blue) and 1 μM (purple) induce an increase in pausing time concentration as small as 0.5 μM and significant changes of all parameters at 1 μM. Figures written inside the bars represent the total number of trajectories. Data are displayed as cumulative probabilities and bar plots with mean values ± s.e.m. in insets. Statistical significance: one star (*) indicate a p value smaller than 0.05 (Wilcoxon and Mann–Whitney two‐tailed test), two stars (**) indicate a p < 0.01 and three stars (***) mean that p < 0.001. (See color plate section for the color representation of this figure.)
6. Figure 6.6 SWCNT reptation dynamics revealed in a complex biocompatible environment, under a more than 20 minutes continuous imaging.
7. Figure 6.7 Super‐resolved map (a) and viscosity map (c) of the extracellular space obtained in acute rat brain slices from the analysis of single SWCNT diffusion. In the central panel (b), the dimensions of the extracellular space ξ could be resolved at resolution smaller than the diffraction limit. (See color plate section for the color representation of this figure.)
Chapter 7
1. Figure 7.1 Schematic of photoacoustic imaging. PA, PhotoAcoustic; US, UltraSound.
2. Figure 7.2 Typical examples of photoacoustic microscopy (PAM). (a) Reflection‐mode optical‐resolution photoacoustic microscopy (OR‐PAM). (b) Dark‐field acoustic‐resolution photoacoustic microscopy (AR‐PAM). (c) Unstained fibroblasts photoacoustic (PA) image superimposed at 422 and 250 nm using OR‐PAM. (d) Coronal (front) PA images processed along the Z‐axis at 850 nm. 1 spleen, 2 carotid artery and jugular vein, 3 subclavian vessels, 4 liver, 5 intestines, 6 cecum, 7 caudal vessels, 8 femoral vessels, 9 popliteal vessels, and 10 mammalian vessels.
3. Figure 7.3 (a) Schematic of cylindrical detection photoacoustic computed tomography (PACT) system (b) Brain and lower abdominal cavity images. (c) Schematic of planar detection photoacoustic computed tomography (PACT) system. (d) In vivo mammalian tissue images in a mouse with a tyrosinase‐based genetic reporter. (e) Schematic of spherical detection photoacoustic computed tomography (PACT) system. (f) Photoacoustic (PA) mammographic images of healthy woman. (g) Schematic of linear detection photoacoustic computed tomography (PACT) system. (h) PA and ultrasound combined images of a human arm. PA, photoacoustic; US, ultrasound, TR, ultrasound transducer; FB, fiber bundle; PC, personal computer; OPO, optical parametric oscillator; UA, ulnar artery; RA, radial artery; T, tendon; GP, gelatin pad.
4. Figure 7.4 (a) Schematic of plain single walled carbon nanotubes (SWNT) and Arg‐Gly‐Asp (RGD) peptide conjugated SWNT‐RGD. (b) Tumor targeting photoacoustic (PA) images after SWCNT‐RGD i.v. injection. (c) PA signal enhancement profiles after SWNT‐RGD and plain SWNT injection. (d) Synthesis of polyethyleneglycol (PEG₄₀₀) coated luminescent carbon nanoparticles (OCN) from commercial grade honey. (e) PA imaging of sentinel lymph nodes after OCN injection. (f) Schematic of NIR dye, pyrrolopyrrole cyanine (PPCy‐C8), loaded perfluorocarbon nanoparticles (PPCy‐C8/PFC). (g) PA images of sentinel lymph nodes after PPCy‐C8/PFC injection, and fluorescent images after PPy‐C8 injection. LN, lymph node; BV, blood vessels. (See color plate section for the color representation of this figure.)
5. Figure 7.5 Multimodal imaging of photoacoustic (PA) and Raman with single‐walled carbon nanotubes (SWCNTs). (a) TEM image of SWCNTs. (b) A Raman spectrum of the SWCNT obtained at 633 nm. (c) Sentinel lymph node PA mapping of a Rat before and after SWCNTs injection; Optical‐resolution photoacoustic microscopy (OR‐PAM) image of the same human breast cancer tissue without (d) and with (e) SWCNTs. (f) Raman spectrum generated from SWCNTs using Raman spectroscopy. (g) In vivo PA imaging of tumor bearing mice after injection of targeting SWCNTs. (h) Ex vivo Raman imaging for verification of SWCNTs with Raman microscope. (See color plate section for the color representation of this figure.)
6. Figure 7.6 Multimodal imaging of photoacoustic (PA) and fluorescent (FL) with carbon nanomaterials. (a) Schematic of CPGA. (b) In vivo NIR FL imaging. and (c) PA imaging of tumor‐bearing mice before and after injection of CPGA. (d) Schematic of indocyanine green conjugated single‐walled carbon nanotubes (ICG‐SWCNT). (e) In vivo Ultrasound (left) and PA images at 80 minutes after injection (right) of ICG‐SWCNT acquired at tumor sites; (f) Ex vivo FL images of ICG‐injected tumor (left) and ICG/SWCNT‐injected tumor (right). (See color plate section for the color representation of this figure.)
7. Figure 7.7 Multimodal imaging of photoacoustic (PA) and computed tomography (CT) imaging with carbon nanomaterials. (a) Schematic of GO/Bi2Se3/PVP nanocomposites. (b) 3D volume rendering CT images before (left) and after (right). (c) CT cross‐sectional images of the tumor site before (top) and after (bottom) intratumoral injection of GO/Bi2Se3/PVP. (d) PA images acquired before and 30 minutes after intratumoral injection of GO/Bi2Se3/PVP.
8. Figure 7.8 (a) Synthesis of nitrogen (N) doped carbon nanodots (N‐CND). (b) Photoacoustic (PA) imaging of sentinel lymph nodes after N‐CND injection. (c) Photothermal therapy (PTT) monitoring after PBS and N‐CND injection with laser irradiation and without irradiation. (d) Synthesis PEGylated graphdiyne (GDY‐PEG). (e) PA imaging of tumor after i.v. injection of GDY‐PEG. (f) PTT monitoring after i.v. injection of GDY‐PEG with laser irradiation and without laser irradiation. (See color plate section for the color representation of this figure.)
9. Figure 7.9 (a) Synthesis of albumin encapsulated Chlorine e6 (Ce6) loaded surface modified single walled carbon nanotube with Evans blue (ACEC). (b‐c) Photoacoustic (PA) and fluorescent imaging of tumor after i.v. injection of Ce6 and ACEC. (d) Photothermal therapy (PTT) and photodynamic therapy (PDT) monitoring. (e) Synthesis of gold nanorod@silica‐carbon dots (GNR@SiO₂‐CDs). (f) PA imaging of tumor after i.v. injection of GNR@SiO₂‐CDs; (g) PTT and PDT monitoring after i.v. injection of GNR@SiO₂‐CDs with laser irradiation of different wavelength (635 nm for PDT, and 808 nm for PTT). (See color plate section for the color representation of this figure.)
Chapter 8
1. Figure 8.1 (a) A diagram (schematic) showing a proposed method of TB biomarker detection using quantum dots. The methodology involves the collection of breath into a Tedlar bag and subsequent mixing into a QDs (or C‐dot) solution. The spectral analysis will be performed for estimation of VOB concentration and prediction of patient health. (b) Absorbance and (c) emission spectra of pristine carbon dots and with different concentrations of VOBs. It can be seen that nicotinate‐CDs solution can be easily distinguished from pristine CDs solution using UV irradiation [44]. (See color plate section for the color representation of this figure.)
2. Figure 8.2 SEM images of (a) random network (RN)‐CNT cast from DMF solution; (b) HBC‐C_6,2 structures cast from 10⁻³ M solution in xylene; and (c) HBC‐C₁₂ structures cast from 10⁴ M solution in toluene. (d) The response to two kinds of HBC‐functionalized RN‐CNT sensors, normalized to the response of the corresponding pristine sensor, to water, methanol, decane, and octane at p _a /p _o = 1. Calibration curves: ΔR/R _b versus analyte concentration (p_a/p_o = 0.05−1). Normalized resistance, ΔR/R _b, of an RN‐CNT sensor before and after the functionalization with a discontinuous HBC‐C₁₂ or HBC‐C_6,2 layer upon exposure to (e) decane, (f) octane, (g) water, and (h) methanol in the vapor phase. All presented values of ΔR/R _b have a signal‐to‐noise ratio greater than 3 [59]. (See color plate section for the color representation of this figure.)
3. Figure 8.3 (a) Schematic diagrams of SERS sensor and overview of the processes involved in the breath. (b) Processed Raman spectra of VOCs biomarker patterns. The biomarker patterns had the same components in breath samples of healthy persons (c) and EGC (b) and AGC (a) patients. (c) PCA of the data set of biomarker patterns of healthy persons (area c) and EGC (area b) and AGC (area a) patients. Each data point in the PCA corresponds to the area of 14 bands in the processed Raman spectra. (d) SERS spectra of simulated and real breath samples of healthy persons (c, c′) and EGC (b, b′) and AGC (a, a′) patients. (e) PCA of the data set of simulated and real breath samples of healthy persons (c, c′) and EGC (b, b′) and AGC (a, a′) patients. Each data point in the PCA corresponds to the area of 14 bands in the SERS spectra [23]. (See color plate section for the color representation of this figure.)
4. Figure 8.4 (a) Optical PL image of GQDs dispersed in water under 365 nm UV lamp; (b) Simulation model explaining the PL mechanism of QGD containing emission of both disordered aromatic core and emission of functional groups; and (c) The response of GQDs to PH under alkaline and acidic conditions [84].
5. Figure 8.5 Illustration of the sensor experimental set‐up with SWCNT‐modified Pt microelectrode as the working electrode (a) and the label‐free electrochemical immunosensor design (b) [94].
6. Figure 8.6 Illustration of the fabrication of DNA immunosensor [88].
7. Figure 8.7 Illustration of the sandwich‐type immunosensor [111]. (a) Photo of the light source, (b) schematics of the photoelectrochemical cell, and (c) schematics of the fabrication of the working electrode. (See color plate section for the color representation of this figure.)
8. Figure 8.8 Illustration of the GO and UCNPs based optical immunosensor [130].
9. Figure 8.9 Illustration of the fabrication of the immunosensor and binding of insulin [143].
Chapter 9
1. Figure 9.1 (a) Synthetic route of CDs. (b) Emission colors of various CDs under UV light exposure. (See color plate section for the color representation of this figure.)
2. Figure 9.2 (a) Optical images of typical CDs illuminated under white (left). and UV (right). light; (b) PL spectra of CDs where red, black, green, and blue lines are the PL spectra for CDs emitting blue, green, yellow, and red fluorescence, respectively; (c) relationship between the size of CDs and their electrochemical properties; (d) HOMO‐LUMO gap dependence on the size of graphitene fragments. (See color plate section for the color representation of this figure.)
3. Figure 9.3 (a) Full survey X‐ray photoelectron spectroscopy (XPS): (b) C 1s, (c) N 1s, and (d) S 2p XPS spectra of S,N‐co‐doped CDs.
4. Figure 9.4 Schematic illustration on the synthesis of P‐CDs and the induced effect due to AIRSE.
5. Figure 9.5 Schematic illustration of pH sensing and bio‐imaging based on two‐photon fluorescence interaction of AE‐TPY bound CDs.
6. Figure 9.6 A schematic illustration of the fabrication and assay procedure that are based on paper origami device. The first step involved patterning paper sheets in bulk using a wax printer as shown in Sheet A, (a) showing 3D origami device without the screen‐printed electrodes. The electrodes on sheet A are screen‐printed in bulk (b, c). The last step involves cutting and folding sheet A into individual 3D origami device (d) and being modified for IgG detection.
7. Figure 9.7 Fluorescence microscopy images (a, b) and their corresponding bright‐field transmission images (c, d) of HeLa cells: (a, c) were incubated with CDs for 24 hours at 37 °C and (b, d) were first incubated with CDs followed by 100 μM of Fe(III). solutions. (See color plate section for the color representation of this figure.)
Chapter 10
1. Figure 10.1 (a) Molecular structure of Ce6. (b) Pictures of supernatants after exfoliation and centrifugation in the presence (left) and absence (right) of Ce6 in H₂O [20]. (See color plate section for the color representation of this figure.)
2. Figure 10.2 Typical AFM image and height profiles of the graphenes after exfoliation with Ce6 [20].
3. Figure 10.3 STEM images of the exfoliated graphene [20].
4. Figure 10.4 Absorption (a) and fluorescence (b, excited at 404 nm) spectra of Ce6 in H₂O before and after the exfoliation of graphene. The absorbance contributed by graphene is indicated as baseline (gray trace) in the absorption spectra (a). Thin and thick arrows indicate the absorbance of Ce6 at Q(I) band and graphene at 660 nm, respectively [20].
5. Figure 10.5 Absorption spectra of the graphene dispersion after 1, 3, and 7 days. The sample used here was prepared under the same conditions as those of the sample used for Figure 10.4. [20].
6. Figure 10.6 (a) Raman spectra of pristine graphite and exfoliated graphene at the laser wavelength of 488 nm. (b) The release profile of Ce6 from G‐Ce6 in PBS at pH 7.4 [20].
7. Figure 10.7 Cell viability of HeLa cells treated with G‐Ce6 or Ce6 at various concentrations without (a) or with (b) irradiation of 660 nm laser for two minutes. Error bars were based on four parallel measurements [20].
8. Figure 10.8 FACS analyses of HeLa cells after incubation with Ce6 and G‐Ce6 at various Ce6 concentrations (0.0062–0.20 μg ml⁻¹ ) for 24 hours [20].
9. Scheme 10.1 Surface engineering on ND50‐PG for conjugation with RGD peptide and Pt(II)‐based drug. (i) Glycidol, 140 °C, 20 hours; (ii) p‐TsCl, pyridine, 0 °C ~ r. t., overnight; (iii) NaN₃, 90 °C, overnight; (iv) succinic anhydride, DMAP, pyridine, 0 °C ~ r. t., overnight; (v) RGD propargyl amide, copper(II) sulfate pentahydrate, sodium ascorbate, r. t., 48 hours; (vi) cisplatin, 0.5 M NaOH, pH 8.0, r. t., 72 hours [21].
10. Scheme 10.2 Synthesis of ND‐PG‐BPP by click chemistry of ND‐PG‐N₃ and BPP with alkynyl group [22].
11. Figure 10.9 FTIR spectra of (A) ND50‐PG, (B) ND‐PG‐OTs, (C) ND‐PG‐N₃, (D) ND‐PG‐N₃‐COOH, (E) ND‐PG‐RGD‐COOH, and (F) ND‐PG‐RGD‐Pt. Arrows indicate new absorption bands in each step [21].
12. Figure 10.10 ¹ H NMR spectra of (A) ND50‐PG, (B) ND‐PG‐OTs, (C) ND‐PG‐N₃ and (D) ND‐PG‐N₃‐COOH in D₂O [21].
13. Figure 10.11 ¹³ C NMR spectra of (A) ND50‐PG, (B) ND‐PG‐OTs, and (C) ND‐PG‐N₃ in D₂O and (D) ND‐PG‐N₃‐COOH in DMSO‐d₆ [21].
14. Figure 10.12 (A) and (B): Cell‐killing effect of cisplatin, ND‐PG‐Pt and ND‐PG‐RGD‐Pt. Concentrations were normalized to platinum up to 20 μg ml⁻¹ . Treatment duration was 24 hours (n = 3). (C) Platinum levels (normalized to protein concentrations) in U87MG and HeLa cells after 24‐hour treatment of cisplatin, ND‐PG‐Pt and ND‐PG‐RGD‐Pt containing 2.5 μg ml⁻¹ of platinum. Values are means ± SD (n = 3). Student's t‐test was performed (* and # p < 0.05, ## p < 0.01) [21].
15. Figure 10.13 FTIR spectra of (a) ND50‐PG, (b) ND‐PG‐OTs,( c) ND‐PG‐N₃, (d) ND‐PG‐Arg₈, (e) ND‐PG‐Lys₈, and (f) ND‐PG‐His₈. Arrows indicate new absorption bands in each step [22].
16. Figure 10.14 Picture of the dispersion of (a) ND50‐PG (20 mg ml⁻¹ ), (b) ND‐PG‐Arg₈, (c) ND‐PG‐Lys₈ and (d) ND‐PG‐His₈ (b – d, 1.0 mg ml⁻¹ ) in water [22]. (See color plate section for the color representation of this figure.)
17. Figure 10.15 Linear relationship (correlation coefficient: 0.98) between pKa of His, Lys, and Arg with zeta potential of ND‐PG‐His₈, ND‐PG‐Lys₈, and ND‐PG‐Arg₈.
18. Figure 10.16 Electrophoretic migration of pDNA, NP (ND50‐PG or ND‐PG‐BPP), and NP / pDNA mixtures at various weight ratios [22].
Chapter 11
1. Figure 11.1 Schematic illustration of different types of carbon nanomaterials.
2. Figure 11.2 The possible ways for the synthesis of graphene derivatives. CRGO: Chemically reduced graphene oxide. TRGO: Thermally reduced graphene oxide. ERGO: Electrochemically reduced graphene oxide.
3. Figure 11.3 Functionalization of graphene‐based nanomaterials for enhanced PTT applications. GO: Graphene oxide. PTT: Photothermal therapy. PDT: Photodynamic therapy.
4. Figure 11.4 The CT imaging of mice after intramuscular injection of GNPs/GO/PLA theranostics. The white arrow points to the injected site. GNPs: Gold nanoparticles. GO: Graphene oxide. PLA: Poly(lactic acid).
5. Figure 11.5 The in vivo bioluminescence and PET imaging with ⁶⁴ Cu‐labeled GO. (a) Serial BLI and its signal intensity in the mice after intravenous injection of cbgLuc‐MDA‐MB‐231 cells. (b) PET imaging of cbgLuc‐MDA‐MB‐231 tumor‐bearing mice after injection of ⁶⁴ Cu‐NOTA‐GO, ⁶⁴ Cu‐NOTA‐GO‐FSHR‐mAb, and ⁶⁴ Cu‐NOTA‐GO‐FSHR‐mAb. (c) The cross‐sectional slices of cbgLuc‐MDA‐MB‐231 tumor‐bearing mice at four hours post‐injection of ⁶⁴ Cu‐NOTA‐GO, ⁶⁴ Cu‐NOTA‐GO‐FSHR‐mAb, and ⁶⁴ Cu‐NOTA‐GO‐FSHR‐mAb. GO: Graphene oxide. BLI: Bioluminescence image. PET: Positron emission tomography. FSHR: Follicle‐stimulating hormone receptor. mAb: Monoclonal antibody. (See color plate section for the color representation of this figure.)
Chapter 12
1. Figure 12.1 Extinction coefficient of a representative tissue [6].
2. Figure 12.2 (a) Structural illustration of GO, which is related to the photothermal properties (oxygen‐containing groups, especially carboxyl group, are related to the dispersibility; aromatic structure is related to the intrinsic absorbance in the NIR region) and (b) NIR absorption of GO (B) [25].
3. Figure 12.3 pH‐mediated cypate‐enhanced photothermal effect of GO [22].
4. Figure 12.4 HSPs expression profile of MCF‐7 cancer cells after NIR illumination treatment [32].
5. Figure 12.5 Semiquantitative biodistribution analysis of NGS‐PEG‐Cy7 in 4T1 tumor‐bearing mice. (a) Spectrally resolved ex vivo fluorescence images of organs before and after injection of NGS‐PEG‐Cy7. SK: skin, M: muscle, I: intestine, H: heart, LU: lung, LI: liver, K: kidney, SP: spleen, ST: stomach, and T: tumor. (b) Semiquantitative biodistribution of NGS‐PEG‐Cy7 in mice determined by the averaged fluorescence intensity of each organ [44]. (See color plate section for the color representation of this figure.)
6. Figure 12.6 (a) Absorbance spectra of SWCNT compared with water [45] and (b) photothermal conversion comparation between SWCNT and MWCNT [46].
7. Figure 12.7 Skin accumulation of SWNTs (a and c) Raman images of a skin slice taken from mice injected with SWNT‐100%‐5kPEG‐PMHC18 and (b and d) SWNT‐10%‐5kPEG‐PMHC18. Overlaid Raman images and hematoxylin and eosin‐stained skin slice images [66].
8. Figure 12.8 In vivo photothermal therapy. Representative photographs of 4T1 tumor bearing mice i.v. injected with either saline or SWNHs/C 18 PMH‐PEG and exposed to laser treatment [60].
9. Figure 12.9 UV‐vis absorption spectra of CDs synthesized from hydrophobic cyanine dye (CyCD) (gray line), cyanine (CyOH) and CyOH aggregated particles [15].
10. Figure 12.10 (a) UV‐vis absorbance spectra and (b) PA amplitude spectrum with different N‐doped CDs [69].
11. Figure 12.11 Hematoxylin and eosin‐stained slices of the heart, liver, spleen, lung, and kidney in mice after PTT. Scale bar: 50 μm [71].
12. Figure 12.12 Photothermal ablation of cancer cells dosed with PHF‐coated silica nanoparticles. (a) Nanoparticle agglomerates (indicated by arrows) in contact with cells before exposure to a 785‐nm laser. (b) Cells appear granulated after five seconds of irradiation. (c) Cells are destroyed after 10 seconds of irradiation, accompanied by bubble formation. (d) Cells (indicated by arrow) adjacent to the irradiated region remain intact [86].
13. Figure 12.13 Treatment of a mice tumor with CP‐0.25 (chitosan‐polyhydroxy fullerenes) nanoparticles. Photographs of mouse tumor (a) two hours and (b) 20 hours after laser irradiation, only a blister was visible after 20 hours (within dotted lines). (c) and (d) Histological sections of remaining tumor stained with hematoxylin and eosin demonstrate areas of necrosis [17]. (See color plate section for the color representation of this figure.)
14. Figure 12.14 (a) UV–Vis absorption spectrum of a. GO, b. GO‐IO, c. GNR, d. GO‐IO‐GNR and (b) temperature variation of five different samples upon laser irradiation [89].