Nanoparticle Probes for Structural and Functional Photoacoustic Molecular Tomography

Abstract

Nowadays, nanoparticle probes have received extensive attention largely due to its potential biomedical applications in structural, functional, and molecular imaging. In addition, photoacoustic tomography (PAT), a method based on the photoacoustic effect, is widely recognized as a robust modality to evaluate the structure and function of biological tissues with high optical contrast and high acoustic resolution. The combination of PAT with nanoparticle probes holds promises for detecting and imaging diseased tissues or monitoring their treatments with high sensitivity. This review will introduce the recent advances in the emerging field of nanoparticle probes and their preclinical applications in PAT, as well as relevant perspectives on future development.

Figure 1

ICG dye-enhanced SWNT probes for photoacoustic imaging. (a) A schematic of a SWNT-ICG particle with ICG molecules (red) attached to the SWNT surface via noncovalent π-π stacking bonds. The targeting peptide was attached to SWNT via a PEGylated phospholipid. (b) The absorption spectra from different probes including SWNT-ICG-RAD (red), plain SWNT (black), and SWNT-ICG-RGD (blue). The absorption intensity of ICG dye-SWNTs particles was much higher (over 20 times) than that of plain SWNT at 780 nm. The absorption spectra between SWNT-ICG-RAD and SWNT-ICG-RGD were very similar, which validated that the peptide conjugation should not significantly perturb the photoacoustic signal. (c) The photoacoustic signals of SWNT-ICG was proportional to the probe concentrations (R ² = 0.9833). Reproduced with permission from [21].

Figure 2

Photoacoustic molecular tomography of deep-embedded targets based on CuS Qdot probes. The agarose gels that contained CuS Qdots were placed in the background of chicken breast muscle with different chicken breasts stacked. (a) showed the configuration of chicken breast muscle stacked. (b) Photograph of chicken breast muscle that had the targets with CuS Qdots of (1) 100 μg/mL (2 OD), (2) 50 μg/mL (1 OD), (3) 25 μg/mL (0.5 OD), (4) 12.5 μg/mL (0.25 OD), (5) 6.25 μg/mL (0.125 OD), (6) gel without contrast agent, and (7) two needle tips at the center and 11 o'clock position. The photoacoustic image was shown at the bottom low with a depth of (c) 25 mm and (d) 50 mm. Reproduced with permission from [22].

Figure 3

Photoacoustic molecular imaging of mice in vivo based on the lanthanide upconversion nanoparticles (UC-α-CD). ((a)–(e)) Generated slice images of live mice before UC-α-CD injection. ((f)–(j)) 35 minutes after injection. Dashed lines in (a) and (f) displayed positions of the mouse while (g)–(j) showed the localized UC-α-CD. (k) 3D rendering of scanned region. (l) Schematic sections related to analysis region. Reproduced with permission from [20].

Figure 4

Photoacoustic molecular imaging of ICG-loaded droplets. (i) Blank droplets in water, (ii) ICG-loaded droplets in water, and (iii) blank droplets in aqueous ICG. The right panel plotted the mean photoacoustic intensity identified in the defined ROI. Error bar represents the mean ± standard deviation. N ≥ 3 for all reported values; scale bar = 2 mm. Reproduced with permission from [23].

Figure 5

Differences on photoacoustic properties generated from conjugated polymer nanoparticles (SPN1), carbon nanotubes (SWCNTs), and gold nanorods (GNRs). (a) The photoacoustic intensity produced by different nanoparticles based on the same mass (25 μg mL⁻¹) (top) and molar (48 nM) (bottom) concentrations in an agar phantom. (b) The photoacoustic intensity regarding indicated nanoparticles in agar phantoms versus the number of laser pulses. (c) The photoacoustic intensity of the nanoparticle-matrigel targets (inclusions) (30 μL) in the subcutaneous dorsal space of living mice as a function of nanoparticle mass concentration. (d) The overlaid photoacoustic/ultrasound images of the nanoparticle-matrigel targets in mice at a concentration of 8 μg mL⁻¹. Reproduced with permission from [24].

Figure 6

In vivo photoacoustic molecular tomography of reactive oxygen species (ROS) generation in a mouse model of acute oedema by using a ratiometric photoacoustic probe (RSPN). (a) The combined photoacoustic/ultrasound images in the thigh of living mice (n = 3) with respect to saline-treated (i) and zymosan-treated (ii) protocols. RSPN was injected into the thigh 20 min after zymosan treatment. (b) The ratio of photoacoustic signals generated between the wavelength of 700 and 820 nm (PA₇₀₀/PA₈₂₀) after RSPN injection. Reproduced with permission from [24].