Towards real-time detection of tumor margins using photothermal imaging of immune-targeted gold nanoparticles

Abstract

Background: One of the critical problems in cancer management is local recurrence of disease. Between 20% and 30% of patients who undergo tumor resection surgery require reoperation due to incomplete excision. Currently, there are no validated methods for intraoperative tumor margin detection. In the present work, we demonstrate the potential use of gold nanoparticles (GNPs) as a novel contrast agent for photothermal molecular imaging of cancer.

Methods: Phantoms containing different concentrations of GNPs were irradiated with continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms.

Results: The results clearly demonstrate the ability to distinguish between cancerous cells specifically targeted with GNPs and normal cells. This technique, which allows highly sensitive discrimination between adjacent low GNP concentrations, will allow tumor margin detection while the temperature increases by only a few degrees Celsius (for GNPs in relevant biological concentrations).

Conclusion: We expect this real-time intraoperative imaging technique to assist surgeons in determining clear tumor margins and to maximize the extent of tumor resection while sparing normal background tissue.

Keywords: gold nanoparticles; molecular imaging; photothermal imaging.

Figure 1

The optical setup.

Figure 2

Left: Absorbance spectra of gold nanospheres (green) and gold nanorods (dashed red). Notes: The wavelengths of the lasers are shown by the arrows. Right: transmission electron microscopy image of 30 nm gold nanospheres (upper figure, scale bar 100 nm) and 25 nm × 65 nm gold nanorods (lower figure, scale bar 100 nm).

Figure 3

Temperature elevation as a function of irradiation time with the 663 nm laser for different concentrations of gold nanorods in aqueous solution. Note: The graph reaches a plateau after approximately 5 seconds.

Figure 4

Temperature elevation as a function of concentrations of gold nanospheres (A) and gold nanorods (B) for the two lasers. Notes: The time point for comparison was after 5 seconds of laser irradiation, when the temperature curves had reached a plateau. The laser optical intensity on the sample was 10 W/cm² for both lasers.

Figure 5

Thermal images of a sample made of two half-cylindrical solid phantoms joined together, one with gold nanorods and the other without. Image (A) was taken before laser irradiation. The border between the phantoms is shown by a dashed straight line. The elliptical contour shows the place where the laser beam hits the sample. Images (B) and (C) were taken after 10 seconds and 5 minutes of laser irradiation, respectively. Note: It can be seen that the temperature in the part of the sample with the gold nanorods rises compared with that in the part without gold nanorods.

Figure 6

Temperature elevation of gold nanorods bioconjugated with an A431 cancer cell line compared with A431 cells without gold nanorods in solution. Notes: It can be seen that the bioconjugated GNR-A431 has a distinctive heating profile compared with the A431 cells.