Near-infrared-resonant gold/gold sulfide nanoparticles as a photothermal cancer therapeutic agent

Abstract

The development and optimization of near-infrared (NIR)-absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing. This work exploits the properties of gold/gold sulfide NIR-absorbing nanoparticles (approximately 35-55 nm) that provide higher absorption (98% absorption and 2% scattering for gold/gold sulfide versus 70% absorption and 30% scattering for gold/silica nanoshells) as well as potentially better tumor penetration. The ability to ablate tumor cells in vitro and efficacy for photothermal cancer therapy is demonstrated, and an in vivo model shows significantly increased long-term, tumor-free survival. Furthermore, enhanced circulation and biodistribution is observed in vivo. This class of NIR-absorbing nanoparticles has the potential to improve upon photothermal tumor ablation for cancer therapy.

Figure 1

TEM images of gold / gold sulfide nanoparticles, (A) before separation – note the presence of triangular nanoprisms, small colloid gold as well as the spherical gold / gold sulfide nanoparticles. (B), after separation using sequential centrifugation, there are very few colloidal gold particles remaining after separation.

Figure 2

Nanoparticles made by self assembly show varying different peak resonances depending on concentration of reactants. A suspension made at a particular ratio of reactants (green curve) is subsequently separated by multiple centrifugation steps to produce a sample with minimal pure gold (530 nm resonance) contamination. Shown below are spectra of gold / gold sulfide nanoparticles after sequential centrifugation separation to remove gold colloid contaminants. The nIR peak of the as-made gold / gold sulfide nanoparticles shifts and narrows after each successive step and as similar species are collected during the process.

Figure 3

Temperature profiles of gold / gold sulfide nanoparticles obtained by heating with a laser and measured using thermocouple.(A) shows maximum temperature of samples after 3 minutes; (B) shows temperature rate increase during first 60 seconds, * p<0.05.

Figure 4

In vitro cellular ablation with bare gold / gold sulfide nanoparticles following incubation and laser application. Yellow circle indicates the laser spot; live/dead stain for viability shows dead cell as red while viable cells appear green. White bars = 200 microns.

Figure 5

Stability testing of PEGylated gold / gold sulfide nanoparticles in 1% saline (+NaCl), controls are without saline (−NaCl); a decrease from 100% indicates aggregation as the peak resonance diminishes during nanoparticle aggregation.

Figure 6

(A) Bio-distribution of nanoparticles in tumored mice. Samples were taken after 24 hour circulation time. Data shows accumulation in the tumors for both types of nanoparticles and higher blood concentration after 24 hours for gold / gold sulfide nanoparticles; (B) Expansion of the y-axis, *p<0.05; (C) Proportion of gold in tumor compared to the liver and spleen for gold / gold sulfide nanoparticles and gold / silica nanoshells. There is a larger amount of gold in the tumor compared to spleen + liver for the gold / gold sulfide nanoparticles, showing better uptake in tumor compared to removal by the RES for these smaller nanoparticles, *p<0.05.

Figure 7

Kaplan - Meier survival of mice following treatment with gold / gold sulfide nanoparticles and laser irradiation. There is a statistically significant increase in survival with 48 hour accumulation compared to 24 hour accumulation for the gold / gold sulfide nanoparticle treated mice and no difference for 48 hour gold / gold sulfide nanoparticle treated mice as compared to gold / silica nanoshell treated mice.