Fig. 6.

(a) Ultrasound images shown in grayscale overlaid with photoacoustic images obtained at 720 nm before and after I.V. administration of EGFR-targeted AuNPs in mouse with A431 EGFR expressing tumor (Group 1). (b) Multi-wavelength photoacoustic images are pseudo-colored to show oxygenated areas in red, deoxygenated areas in blue, and molecular specific interactions between Au NPs and cancer cells in orange. H&E stain (c) and Silver stain (d) of tumor section taken at the imaging cross-section after injection of AuNPs Dark regions in the silver stained section show the presence of AuNPs. There is a clear time-dependent increase in the photoacoustic signal at 720 nm after I.V injection of EGFR-targeted AuNPs indicating receptor-mediated aggregation of AuNPs in cellular endosomes. The aggregation leads to plasmon resonance coupling between AuNPs that results in a red-shift in optical absorption of the nanoparticles. As photoacoustic signal is proportional to optical absorption of the tissue, a time-dependent increase in photoacoustic signal is observed due to the plasmon resonance coupling effect. 3-D Ultrasound (grayscale) and overlaid photoacoustic images (red scale) of an EGFR-expressing tumor (e) before and (f) 4 h after administration of EGFR-targeted gold nanoparticles. The bounding box represents a 12 mm × 12 mm × 13.3 mm field of view. A heterogeneous distribution of the PA signal associated with receptor-mediated endocytosis of AuNPs in the tumor is clearly visible in (f).