Plasmonic Nanoparticles for Photothermal Therapy: Benchmarking of Photothermal Properties and Modeling of Heating at Depth in Human Tissues

Abstract

Many different types of nanoparticles have been developed for photothermal therapy (PTT), but directly comparing their efficacy as heaters and determining how they will perform when localized at depth in tissue remains complex. To choose the optimal nanoparticle for a desired hyperthermic therapy, it is vital to understand how efficiently different nanoparticles extinguish laser light and convert that energy to heat. In this paper, we apply photothermal mass conversion efficiency (η _m ) as a metric to compare nanoparticles of different shapes, sizes, and conversion efficiencies. We selected silica-gold nanoshells (AuNShells), gold nanorods (AuNRs), and gold nanostars (AuNStars) as three archetypal nanoparticles for PTT and measured the η _m of each to demonstrate the importance of considering both photothermal efficiency and extinction cross section when comparing nanoparticles. By utilizing a Monte Carlo model, we further applied η _m to model how AuNRs performed when located at tissue depths of 0-30 mm by simulating the depth penetration of near-infrared (NIR) laser light. These results show how nanoparticle concentration, laser power, and tissue depth influence the ramp time to a hyperthermic temperature of 43 °C. The methodology outlined in this paper creates a framework to benchmark the heating efficacy of different nanoparticle types and a means of estimating the feasibility of nanoparticle-mediated PTT at depth in the NIR window. These are key considerations when predicting the potential clinical impact in the early stages of nanoparticle design.

Figure 1

UV–vis extinction spectra of (A) AuNShells, (B) AuNRs, and (C) AuNStars. The red dashed line indicates the laser wavelength used for PTT (808 nm). TEM image of (D) AuNShell, (E) AuNRs, and (F) AuNStars. All TEM images were collected at the same magnification.

Figure 2

(A) Schematic of the experimental setup, all three suspensions were diluted to an extinction value of 0.1 at 808 nm. (B) The intensity of light scattered by AuNShells, AuNRs, and AuNStars during 10 ms 808 nm laser exposure at 500 mW power. (C) The temperature increase of the nanoparticle suspensions and blank relative to ambient temperature upon exposure to laser at 1 W. (D) Photothermal conversion efficiency of the nanoparticles (SD of 3 technical repeats).

Figure 3

(A) Relative temperature increase of the three nanoparticle suspensions and a water blank during the first 60 s of laser irradiation (808 nm, 500 mW). The solid line is the mean and shading is the SD of 3 technical repeats. (B) Photothermal mass conversion efficiency of AuNShells, AuNRs, and AuNStars. Error bars indicate the SD of 3 technical repeats and SD in gold mass concentrations.

Figure 4

(A) Heat map of simulated photon penetration into breast tissue. Photon density is presented as a fraction of the dose delivered to the tissue surface. (B) Relative photon density at depths of 0–30 mm for distances laterally translated from the optical axis (center of the laser spot) by 0, 4.8, 5.9, and 11 mm.