Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice

Abstract

Plasmonic photothermal therapy (PPTT) is a minimally-invasive oncological treatment strategy in which photon energy is selectively administered and converted into heat sufficient to induce cellular hyperthermia. The present work demonstrates the feasibility of in vivo PPTT treatment of deep-tissue malignancies using easily-prepared plasmonic gold nanorods and a small, portable, inexpensive near-infrared (NIR) laser. Dramatic size decreases in squamous cell carcinoma xenografts were observed for direct (P<0.0001) and intravenous (P<0.0008) administration of pegylated gold nanorods in nu/nu mice. Inhibition of average tumor growth for both delivery methods was observed over a 13-day period, with resorption of >57% of the directly-injected tumors and 25% of the intravenously-treated tumors.

Fig. 1

Histological sections of silver stained HSC-3 tumor xenografts from female nu/nu mice intravenously (tail) injected with (a) 100 μL of 10 mM PBS following 24 hr circulation and pegylated gold nanorods (100 μL, OD_λ=800=120) following (b) 2 hr (c), 6 hr, and (d) 24 hr accumulation. Direct injection of particles to the tumor interstitium was used as a positive staining control (data not shown). Arrow indicates staining of red blood cells (observed in all tumors).

Fig. 2

NIR transmission images of mice prior to PPTT treatments. Inset shows intensity line-scans of NIR extinction at tumor sites for control ( ), intravenous ( ), and direct ( ) administration of pegylated gold nanorods. Control mice were interstitially injected with 15 μL 10 mM PBS alone, while directly administered mice received interstitial injections of 15 μL pegylated gold nanorods (OD_λ=800=40, 2 min accumulation), and intravenously administered mice recieved 100 μL pegylated gold nanorod (OD_λ=800=120, 24 hr accumulation) injections.

Fig. 3

Thermal transient measurements of HSC-3 tumor interstitia during (a) direct and (b) intravenous near-infrared PPTT ( ) and sham/NIR ( ) treatments using pegylated gold nanorods. Direct PPTT treatments were performed by administration of 15 μL pegylated gold nanorods (OD_λ=800=40, 2 min accumulation) followed by 10 min of 0.9–1.1 W/cm² NIR laser exposure. Intravenous PPTT treatments were performed by administration of 100 μL pegylated gold nanorods (OD_λ=800=120, 24 hr accumulation) followed by 10 min of 1.7–1.9 W/cm² NIR laser exposure. Sham/NIR treatments were performed by administration of 15 μL 10 mM PBS and NIR laser exposure of comperable time and power density. Errors reported as standard deviation.

Fig. 4

Average change in tumor volume for HSC-3 xenografts following near-infrared PPTT treatment by control ( ), intravenous ( ), and direct ( ) injection of pegylated gold nanorods. Errors for control (n=10), direct injection (n=8), and intravenous injection (n=7) groups reported as standard error of the means. Control mice were treated by interstitial injection of 15 μL 10 mM PBS alone, while intravenous PPTT treatments were performed by administration of 100 μL pegylated gold nanorods (OD_λ=800=120, 24 hr accumulation) followed by 10 min of 1.7–1.9 W/cm² NIR laser exposure. Direct PPTT treatments were performed by administration of 15 μL pegylated gold nanorods (OD_λ=800=40, 2 min accumulation) followed by 10 min of 0.9–1.1 W/cm² NIR laser exposure.