Gold nanocages as contrast agents for photoacoustic imaging

Abstract

Gold nanoparticles with tunable absorption and scattering properties have been developed as contrast agents for various optical imaging techniques. As a hybrid modality that combines the merits of both optical and ultrasonic imaging, photoacoustic (PA) imaging also benefits from the use of these nanoparticles to greatly enhance the contrast for visualization of structures and biomarkers in biological tissues. Gold nanocages characterized by hollow interiors, ultrathin and porous walls are of particular interest for in vivo PA imaging because of their compact sizes, bio-inertness and well-defined surface chemistry, as well as their strong and highly wavelength-tunable optical absorption in the near-infrared (NIR) optical window of soft tissues. This review discusses the application of gold nanocages as a new class of contrast agents for PA imaging in the context of cancer diagnosis.

Figure 1.

SEM images of (A) Ag nanocubes and (B) AuNCs. The inset shows the corresponding TEM images of the same sample. (C) UV–vis spectra of the samples obtained by titrating Ag nanocubes with different volumes of 0.1 mM HAuCl₄ solution.

Figure 2.

(top) An experimental setup of a PA imaging system; (bottom) a typical depth-resolved B-scan PA image (x-z scan) of a suspension of AuNCs at three different concentrations. Reproduced with permission from (29), copyright 2009 American Chemical Society.

Figure 3.

(A) The measured PA signal amplitude generated with and without AuNCs in rat blood at several wavelengths. Noninvasive PA imaging of a rat’s cerebral cortex (B) before the injection of AuNCs and (C) about 2h after the final injection of nanocages, which is the peak enhancement point. Reproduced with permission from (35), copyright 2007 American Chemical Society.

Figure 4.

PA images of the axillary region of a rat taken (A) before and (B) 28 min after the injection of AuNCs. (C) The changes of PA signal amplitude as a function of the post‐injection time. After the injection, PA signals increased with time, which means gradual accumulations of the nanocages. (D-F) Depth capability of SLN mapping with AuNCs. The PA images were acquired after the injection of nanocages for: (D) 126 min with a total imaging depth of 10mm by placing a layer of chicken breast tissue on the axillary region; (E) 165 min with a total imaging depth of 21mm by adding another layer of chicken breast tissue; and (F) 226 min with a total imaging depth of 33mm by using three layers of chicken breast tissue. The bars represent the optical absorption. BV, blood vessel. SLN, sentinel lymph node. Reproduced with permission from (36), copyright 2009 American Chemical Society.

Figure 5.

In vivo noninvasive PA time-course coronal MAP images of B16 melanomas using [Nle⁴, d-Phe⁷]-α-MSH- and PEG-AuNCs. (A, E) a schematic of the [Nle⁴, d-Phe⁷]-α-MSH- and PEG-AuNCs. Time-course PA images of the B16 melanomas after intravenous injection with 100 μl of 10 nM (B-D) [Nle⁴, d-Phe⁷]-α-MSH- and (F-H) PEG-AuNCs through the tail vein. The background vasculature images were obtained using the PA microscope at 570 nm (ultrasonic frequency = 50 MHz), and the melanoma images were obtained using the PA macroscope at 778 nm (ultrasonic frequency = 10 MHz). Reproduced with permission from (46), copyright 2010 American Chemical Society.

Figure 6.

(A) Increase of PA amplitude in the melanoma tumors after intravenous injection of [[Nle⁴, d-Phe⁷]-α-MSH-AuNCs and PEG-AuNCs (n = 4 mice for each group), respectively, for different periods of time. The PA signals increased up to 38 ± 6% for [Nle⁴, d-Phe⁷]-α-MSH-AuNCs while the maximum signal increase only reached 13 ± 2% for PEG-AuNCs at a post-injection time of 6h (p <0.0001). (B) The average number of AuNCs accumulated in the melanomas dissected at 6h post-injection for the two types of AuNCs as measured by ICP-MS. Here N_tumor denotes the number of AuNCs per unit tumor mass (g). Reproduced with permission from (46), copyright 2010 American Chemical Society.