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Photoacoustic (PA) imaging can provide real-time changes with high spatial resolution. This technology combines the contrast and spectral sensitivities of optical imaging with the resolution and tissue penetration abilities of ultrasound. Materials absorb light energy and convert it into heat energy by a nonradiative relaxation mechanism. On exposure to heat the materials expand due to their thermoelastic properties generating a pressure wave. This pressure wave in turn helps detection, in the course of its dissemination process through the surrounding environment onto the surface. The conversion oflight into heat energy results in generation ofsound waves and thus the term, photoacoustic [88]. Bayer et al. tuned gold nanorods (GNR) by coating the construct with amorphous silica, which improves thermal stability and PA signal generation efficiency [89—91]. The optical absorption spectra of GNR can be tuned to exhibit different absorption wavelengths that help distinguish multiple CAs through multiwavelength PA imaging [91]. Similarly, Rich et al. demonstrate the potential clinical utility of PA imaging for visualization of cancer in salivary gland [92]. Silica-coated GNR (SIO2- GNR) with peak absorption wavelengths at 780 and 830 nm were targeted to cells expressing two receptors, EGFR and HER2. Cells incubated with target-specific SIO2-GNR were inserted into a phantom tissue and imaged with PA technology. The authors reported enhanced PA signal in cells targeted with SIO2-GNR relative

Table 14.3 Different types of gold nanoparticles used for photoacoustic imaging


Size, shape, and symmetry

Absorption spectrum



Gold nanoshells

Dielectric core coated by a metallic shell; Core 50 nm, shell 3.2 nm

600—900 nm [visible—near infrared (NIR) region]

  • 1. Minimal absorption and maximal optical penetration
  • 2. Resistance to thermal denaturation and bleaching

[63], [94], [95]

Gold nanorods

Cylindrical shape, width 20 nm, length 6.6 nm

600—900 nm (visible-NIR region)

Effective in targeting specific cellular receptors


Gold nanocages

Cuboidal; inner edges length of 50 nm, thickness of wall 6 nm

600—900 nm (visible-NIR region)

  • 1. Gold nanocages can enhance images on integration with optical coherence tomography for resolving tissue microanatomy
  • 2. Immunotargeting moieties capable of photothermal destruction of cancer cells in vitro

[95], [96], [97]

Indocyanine green doped

100 nm

700—2500 nm (NIR region)

  • 1. Photosensitizer (PS) that can produce singlet oxygen via energy transfer from dye to oxygen molecule
  • 2. PS effective in photodynamic therapy
  • 3. Dye encapsulated in nanoparticles prolong circulation time

[95], [98]

to non-SIOg-GNR-coated construct [91]. Description of PA signal detection with a custom-built system that acquires images by a combination of ultrasound and PA signals can be found elsewhere [91].

Bayer et al. demonstrated the efficacy of PA technology in vivo by injecting SIO2-GNR particles into a breast cancer murine model overexpressing HER2 and avb3 receptors. The researchers reported high-resolution 3D anatomical images of the tumor region with a combination of PA and ultrasound technology. Interestingly, this study determined tumor growth by functional PA imaging of blood oxygen saturation. By assessing the levels of oxygen saturation, hypoxic regions within tumor region can be mapped with this robust technology [88]. This imaging system has the potential to provide unique information on prognosis and individualized response to therapy.

Agarwal et al. prepared GNRs conjugated to tumor necrosis factor (TNF-a) antibody and radiolabeled with I to monitor anti-rheumatic drug delivery. A combination of dual modalities, PA and nuclear imaging through one CA comprising GNRs, is able to capture images of deep and mineralized tissue joints of rat tail in situ. This technology has the capability to track GNRs down to a concentration of 10 pm with a minimal radiolabeling of 5 pCi [77]. Chamberland et al., demonstrated PA tomography (PAT) of joints to monitor drug delivery non-invasively [93]. GNRs conjugated to molecules that inhibit TNF (etanercept) were injected intraarticularly in mice. PAT of tail joints ex vivo was performed to acquire images of GNR- conjugated etanercept molecules. The system was able to capture images down to concentrations of 1 pm in phantom tissues and 10 pM in biological samples with high spatial resolution and excellent signal-to-noise ratio [93]. An overview on different types of gold nanoparticles used in PA imaging and their properties are summarized Table 14.3.

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