Recent Advances in Molecular Imaging with Gold Nanoparticles

Abstract

Gold nanoparticles (AuNP) have been extensively developed as contrast agents, theranostic platforms, and probes for molecular imaging. This popularity has yielded a large number of AuNP designs that vary in size, shape, surface functionalization, and assembly, to match very closely the requirements for various imaging applications. Hence, AuNP based probes for molecular imaging allow the use of computed tomography (CT), fluorescence, and other forms of optical imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI), and other newer techniques. The unique physicochemical properties, biocompatibility, and highly developed chemistry of AuNP have facilitated breakthroughs in molecular imaging that allow the detection and imaging of physiological processes with high sensitivity and spatial resolution. In this Review, we summarize the recent advances in molecular imaging achieved using novel AuNP structures, cell tracking using AuNP, targeted AuNP for cancer imaging, and activatable AuNP probes. Finally, the perspectives and current limitations for the clinical translation of AuNP based probes are discussed.

Figure 1.

A) TEM of biodegradable PCPP nanospheres loaded with small gold nanoparticles. In vivo imaging with B) CT and C) PAI. D) Degradation of PCPP nanospheres loaded with either glutathione-coated gold nanoparticles (Glu-Au-PCPP) or 11-mercaptoundecanoic acid (11MUA-Au-PCPP) in 10% serum at 37 °C. Adapted with permission from reference [9].

Figure 2.

A) Schematic for gold nano-assemblies preparation and subsequent in vivo fluorescence imaging. TEM micrographs of B) free AuNCs/PPI NPs and C) AuNC/PPI@RBC complexes. Scale bar = 50 nm. D) In vivo fluorescence imaging of mice injected with different nanoparticle formulations to show prolonged circulation time and enhanced tumor accumulation from RBC coated nanoparticles. Adapted with permission from reference [].

Figure 3.

A) Schematic depiction of AuNP-PLL complex. B) TEM of AuNP complexed with PLL and RITC. C) TEM of internalized AuNP in hMSC. D) In vitro microCT images of 1 × 10⁶ hMSCs labeled with different concentration of AuNP-PLL complex. E) In vivo microCT images of labeled hMSCs injected in the striatum at different cell doses: (1) 5 × 10⁵ cells, (2) 2 × 10⁵ cells, (3) 6 × 10⁴ cells, (4) 2 × 10⁴ cells (HU = 76), (5) brain parenchyma, and (6) skull. F) Immunofluorescent images of the injection site (1) in panel (E). Left: transplanted hMSCs; middle: RITC in AuNP-PLL complex; right: overlay image of left and middle images. Scale bar = 200 μm. Adapted with permission from reference [].

Figure 4.

A) In vivo non-background-corrected maximum intensity projection (MIP) PA images of a mouse at t = 6 and 24 h post-injection of both targeted and non-targeted AuNP. Corresponding PA signal intensity values at various time points from B) targeted AuNP and C) non-targeted AuNP. Adapted with permission from reference [].

Figure 5.

A) Schematic of the production of plasmonic nanogels and their degradation triggered by ROS. Representative TEM images of the PPB NP B) maintaining their structure in H₂O, C) degraded upon exposure to H₂O₂. Influence of stimulation induced ROS overproduction in macrophages upon incubation with the ROS sensitive PPB NP and the control PCPP NP by D) PAI, E) CT contrast, F) contrast enhancement expressed as percentages in CT (blue) and PAI (red). Adapted with permission from reference [].

Figure 6.

Schematic and representative TEM images of A) synthesized AuNR, B) Au/AgNRs upon Ag deposition, C) AuNR following Ag⁺ etching. Comparative ultrasound (gray scale) and photoacoustic (red scale) images of mice injected with D) Au/AgNR followed by silver etchant, and E) Au/AgNR. Adapted with permission from reference [].